Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids

Author(s): Daniele Bottai, Raffaella Adami, Rita Paroni and Riccardo Ghidoni*

Volume 27 , Issue 24 , 2020

Page: [4039 - 4061] Pages: 23

DOI: 10.2174/0929867326666190506120213

Price: $65


Almost no neurological disease exists without microglial activation. Microglia has exert a pivotal role in the maintenance of the central nervous system and its response to external and internal insults. Microglia have traditionally been classified as, in the healthy central nervous system, “resting”, with branched morphology system and, as a response to disease, “activated”, with amoeboid morphology; as a response to diseases but this distinction is now outmoded. The most devastating disease that hits the brain is cancer, in particular glioblastoma. Glioblastoma multiforme is the most aggressive glioma with high invasiveness and little chance of being surgically removed. During tumor onset, many brain alterations are present and microglia have a major role because the tumor itself changes microglia from the pro-inflammatory state to the anti-inflammatory and protects the tumor from an immune intervention.

What are the determinants of these changes in the behavior of the microglia? In this review, we survey and discuss the role of sphingolipids in microglia activation in the progression of brain tumors, with a particular focus on glioblastoma.

Keywords: Ceramide, inflammation, ganglioside, brain tumor, microglia-tumor interaction, microglia activation.

Thudichum, J.L.W. A Treatise on the Chemical Constituents of the Brain (a fascimile edition of the original); Bailliere: London, 1962.
Merrill, A.H., Jr; Sullards, M.C. Opinion article on lipidomics: Inherent challenges of lipidomic analysis of sphingolipids. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2017, 1862(8), 774-776.
[] [PMID: 28161582]
Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H., Jr; Murphy, R.C.; Raetz, C.R.; Russell, D.W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M.S.; White, S.H.; Witztum, J.L.; Dennis, E.A. A comprehensive classification system for lipids. J. Lipid Res., 2005, 46(5), 839-861.
[] [PMID: 15722563]
Hannun, Y.A.; Obeid, L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol., 2018, 19(3), 175-191.
[] [PMID: 29165427]
Lahiri, S.; Futerman, A.H. The metabolism and function of sphingolipids and glycosphingolipids. Cell. Mol. Life Sci., 2007, 64(17), 2270-2284.
[] [PMID: 17558466]
Gault, C.R.; Obeid, L.M.; Hannun, Y.A. An overview of sphingolipid metabolism: from synthesis to breakdown. Adv. Exp. Med. Biol., 2010, 688, 1-23.
[] [PMID: 20919643]
Groux-Degroote, S.; Guérardel, Y.; Delannoy, P. Gangliosides: structures, biosynthesis, analysis, and roles in cancer. ChemBioChem, 2017, 18(13), 1146-1154.
[] [PMID: 28295942]
Huwiler, A.; Kolter, T.; Pfeilschifter, J.; Sandhoff, K. Physiology and pathophysiology of sphingolipid metabolism and signaling. Biochim. Biophys. Acta, 2000, 1485(2-3), 63-99.
[] [PMID: 10832090]
Futerman, A.H.; Riezman, H. The ins and outs of sphingolipid synthesis. Trends Cell Biol., 2005, 15(6), 312-318.
[] [PMID: 15953549]
Tettamanti, G.; Bassi, R.; Viani, P.; Riboni, L. Salvage pathways in glycosphingolipid metabolism. Biochimie, 2003, 85(3-4), 423-437.
[] [PMID: 12770781]
Maceyka, M.; Spiegel, S. Sphingolipid metabolites in inflammatory disease. Nature, 2014, 510(7503), 58-67.
[] [PMID: 24899305]
Yamaji, T.; Hanada, K. Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins. Traffic, 2015, 16(2), 101-122.
[] [PMID: 25382749]
Kitatani, K.; Idkowiak-Baldys, J.; Hannun, Y.A. The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell. Signal., 2008, 20(6), 1010-1018.
[] [PMID: 18191382]
Yuyama, K.; Sun, H.; Mitsutake, S.; Igarashi, Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J. Biol. Chem., 2012, 287(14), 10977-10989.
[] [PMID: 22303002]
Zhang, H.; Desai, N.N.; Olivera, A.; Seki, T.; Brooker, G.; Spiegel, S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J. Cell Biol., 1991, 114(1), 155-167.
[] [PMID: 2050740]
Obeid, L.M.; Linardic, C.M.; Karolak, L.A.; Hannun, Y.A. Programmed cell death induced by ceramide. Science, 1993, 259(5102), 1769-1771.
[] [PMID: 8456305]
Hagen, N.; Hans, M.; Hartmann, D.; Swandulla, D.; van Echten-Deckert, G. Sphingosine-1-phosphate links glycosphingolipid metabolism to neurodegeneration via a calpain-mediated mechanism. Cell Death Differ., 2011, 18(8), 1356-1365.
[] [PMID: 21331079]
Hahn, C.; Tyka, K.; Saba, J.D.; Lenzen, S.; Gurgul-Convey, E. Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity. J. Biol. Chem., 2017, 292(49), 20292-20304.
[] [PMID: 29070677]
Mathias, S.; Kolesnick, R. Ceramide: a novel second messenger. Adv. Lipid Res., 1993, 25, 65-90.
[PMID: 8368154]
Siskind, L.J.; Kolesnick, R.N.; Colombini, M. Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J. Biol. Chem., 2002, 277(30), 26796-26803.
[] [PMID: 12006562]
Gulbins, E. Regulation of death receptor signaling and apoptosis by ceramide. Pharmacol. Res., 2003, 47(5), 393-399.
[] [PMID: 12676513]
Chipuk, J.E.; McStay, G.P.; Bharti, A.; Kuwana, T.; Clarke, C.J.; Siskind, L.J.; Obeid, L.M.; Green, D.R. Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell, 2012, 148(5), 988-1000.
[] [PMID: 22385963]
Saddoughi, S.A.; Ogretmen, B. Diverse functions of ceramide in cancer cell death and proliferation. Adv. Cancer Res., 2013, 117, 37-58.
[] [PMID: 23290776]
Sentelle, R.D.; Senkal, C.E.; Jiang, W.; Ponnusamy, S.; Gencer, S.; Selvam, S.P.; Ramshesh, V.K.; Peterson, Y.K.; Lemasters, J.J.; Szulc, Z.M.; Bielawski, J.; Ogretmen, B. Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat. Chem. Biol., 2012, 8(10), 831-838.
[] [PMID: 22922758]
Salazar, M.; Carracedo, A.; Salanueva, I.J.; Hernández-Tiedra, S.; Lorente, M.; Egia, A.; Vázquez, P.; Blázquez, C.; Torres, S.; García, S.; Nowak, J.; Fimia, G.M.; Piacentini, M.; Cecconi, F.; Pandolfi, P.P.; González-Feria, L.; Iovanna, J.L.; Guzmán, M.; Boya, P.; Velasco, G. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Invest., 2009, 119(5), 1359-1372.
[] [PMID: 19425170]
Ogretmen, B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer, 2018, 18(1), 33-50.
[] [PMID: 29147025]
Parham, K.A.; Zebol, J.R.; Tooley, K.L.; Sun, W.Y.; Moldenhauer, L.M.; Cockshell, M.P.; Gliddon, B.L.; Moretti, P.A.; Tigyi, G.; Pitson, S.M.; Bonder, C.S. Sphingosine 1-phosphate is a ligand for peroxisome proliferator-activated receptor-γ that regulates neoangiogenesis. FASEB J., 2015, 29(9), 3638-3653.
[] [PMID: 25985799]
Chalfant, C.E.; Spiegel, S. Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J. Cell Sci., 2005, 118(Pt 20), 4605-4612.
[] [PMID: 16219683]
Boujaoude, L.C.; Bradshaw-Wilder, C.; Mao, C.; Cohn, J.; Ogretmen, B.; Hannun, Y.A.; Obeid, L.M. Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J. Biol. Chem., 2001, 276(38), 35258-35264.
[] [PMID: 11443135]
Mitra, P.; Oskeritzian, C.A.; Payne, S.G.; Beaven, M.A.; Milstien, S.; Spiegel, S. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl. Acad. Sci. USA, 2006, 103(44), 16394-16399.
[] [PMID: 17050692]
Fu, P.; Ebenezer, D.L.; Ha, A.W.; Suryadevara, V.; Harijith, A.; Natarajan, V. Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine-1-phosphate signaling in epigenetic regulation of inflammation and gene expression. J. Cell. Biochem., 2018, 119(8), 6337-6353.
[] [PMID: 29377310]
Zeng, G.; Yu, R.K. Cloning and transcriptional regulation of genes responsible for synthesis of gangliosides. Curr. Drug Targets, 2008, 9(4), 317-324.
[] [PMID: 18393825]
van Echten-Deckert, G.; Herget, T. Sphingolipid metabolism in neural cells. Biochim. Biophys. Acta, 2006, 1758(12), 1978-1994.
[] [PMID: 16843432]
Bottai, D.; Adami, R.; Ghidoni, R. The crosstalk between glycosphingolipids and neural stem cells. J. Neurochem., 2019, 148(6), 698-711.
[] [PMID: 30269334]
Sierra, A.; de Castro, F.; Del Río-Hortega, J.; Rafael Iglesias-Rozas, J.; Garrosa, M.; Kettenmann, H. The “Big-Bang” for modern glial biology: Translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. Glia, 2016, 64(11), 1801-1840.
[] [PMID: 27634048]
Ginhoux, F.; Greter, M.; Leboeuf, M.; Nandi, S.; See, P.; Gokhan, S.; Mehler, M.F.; Conway, S.J.; Ng, L.G.; Stanley, E.R.; Samokhvalov, I.M.; Merad, M. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science, 2010, 330(6005), 841-845.
[] [PMID: 20966214]
Gomez Perdiguero, E.; Klapproth, K.; Schulz, C.; Busch, K.; Azzoni, E.; Crozet, L.; Garner, H.; Trouillet, C.; de Bruijn, M.F.; Geissmann, F.; Rodewald, H.R. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature, 2015, 518(7540), 547-551.
[] [PMID: 25470051]
Iturri, L.; Saenz Coronilla, J.; Lallemand, Y.; Gomez Perdiguero, E. Identification of erythromyeloid progenitors and their progeny in the mouse embryo by flow cytometry. J Vis Exp, 2017, 125.
[] [PMID: 28745620]
Kierdorf, K.; Prinz, M. Microglia in steady state. J. Clin. Invest., 2017, 127(9), 3201-3209.
[] [PMID: 28714861]
Badie, B.; Schartner, J.M. Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery, 2000, 46(4), 957-961.
[PMID: 10764271]
Hanisch, U.K.; Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci., 2007, 10(11), 1387-1394.
[] [PMID: 17965659]
Gómez-Nicola, D.; Valle-Argos, B.; Pita-Thomas, D.W.; Nieto-Sampedro, M. Interleukin 15 expression in the CNS: blockade of its activity prevents glial activation after an inflammatory injury. Glia, 2008, 56(5), 494-505.
[] [PMID: 18240307]
Gomez-Nicola, D.; Valle-Argos, B.; Nieto-Sampedro, M. Blockade of IL-15 activity inhibits microglial activation through the NFkappaB, p38, and ERK1/2 pathways, reducing cytokine and chemokine release. Glia, 2010, 58(3), 264-276.
[] [PMID: 19610094]
Lisi, L.; Stigliano, E.; Lauriola, L.; Navarra, P.; Dello Russo, C. Proinflammatory-activated glioma cells induce a switch in microglial polarization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells. ASN Neuro, 2014, 6(3), 171-183.
[] [PMID: 24689533]
Ginhoux, F.; Prinz, M. Origin of microglia: current concepts and past controversies. Cold Spring Harb. Perspect. Biol., 2015, 7(8)a020537
[] [PMID: 26134003]
Hambardzumyan, D.; Gutmann, D.H.; Kettenmann, H. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci., 2016, 19(1), 20-27.
[] [PMID: 26713745]
Dekkers, M.P.; Barde, Y.A. Developmental biology. Programmed cell death in neuronal development. Science, 2013, 340(6128), 39-41.
[] [PMID: 23559240]
Dekkers, M.P.; Nikoletopoulou, V.; Barde, Y.A. Cell biology in neuroscience: Death of developing neurons: new insights and implications for connectivity. J. Cell Biol., 2013, 203(3), 385-393.
[] [PMID: 24217616]
Ashwell, K. Microglia and cell death in the developing mouse cerebellum. Brain Res. Dev. Brain Res., 1990, 55(2), 219-230.
[] [PMID: 2253324]
Witting, A.; Müller, P.; Herrmann, A.; Kettenmann, H.; Nolte, C. Phagocytic clearance of apoptotic neurons by Microglia/Brain macrophages in vitro: involvement of lectin-, integrin-, and phosphatidylserine-mediated recognition. J. Neurochem., 2000, 75(3), 1060-1070.
[] [PMID: 10936187]
Marín-Teva, J.L.; Dusart, I.; Colin, C.; Gervais, A.; van Rooijen, N.; Mallat, M. Microglia promote the death of developing Purkinje cells. Neuron, 2004, 41(4), 535-547.
[] [PMID: 14980203]
Ueno, M.; Fujita, Y.; Tanaka, T.; Nakamura, Y.; Kikuta, J.; Ishii, M.; Yamashita, T. Layer V cortical neurons require microglial support for survival during postnatal development. Nat. Neurosci., 2013, 16(5), 543-551.
[] [PMID: 23525041]
Bottai, D.; Fiocco, R.; Gelain, F.; Defilippis, L.; Galli, R.; Gritti, A.; Vescovi, L.A. Neural stem cells in the adult nervous system. J. Hematother. Stem Cell Res., 2003, 12(6), 655-670.
[] [PMID: 14977475]
Adami, R.; Pagano, J.; Colombo, M.; Platonova, N.; Recchia, D.; Chiaramonte, R.; Bottinelli, R.; Canepari, M.; Bottai, D. Reduction of movement in neurological diseases: effects on neural stem cells characteristics. Front. Neurosci., 2018, 12, 336.
[] [PMID: 29875623]
Cunningham, C.L.; Martínez-Cerdeño, V.; Noctor, S.C. Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J. Neurosci., 2013, 33(10), 4216-4233.
[] [PMID: 23467340]
Lawson, L.J.; Perry, V.H.; Dri, P.; Gordon, S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience, 1990, 39(1), 151-170.
[] [PMID: 2089275]
Abiega, O.; Beccari, S.; Diaz-Aparicio, I.; Nadjar, A.; Layé, S.; Leyrolle, Q.; Gómez-Nicola, D.; Domercq, M.; Pérez-Samartín, A.; Sánchez-Zafra, V.; Paris, I.; Valero, J.; Savage, J.C.; Hui, C.W.; Tremblay, M.E.; Deudero, J.J.; Brewster, A.L.; Anderson, A.E.; Zaldumbide, L.; Galbarriatu, L.; Marinas, A.; Vivanco, Md.; Matute, C.; Maletic-Savatic, M.; Encinas, J.M.; Sierra, A. Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling. PLoS Biol., 2016, 14(5)e1002466
[] [PMID: 27228556]
Sierra, A.; Encinas, J.M.; Deudero, J.J.; Chancey, J.H.; Enikolopov, G.; Overstreet-Wadiche, L.S.; Tsirka, S.E.; Maletic-Savatic, M. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 2010, 7(4), 483-495.
[] [PMID: 20887954]
Gertig, U.; Hanisch, U.K. Microglial diversity by responses and responders. Front. Cell. Neurosci., 2014, 8, 101.
[] [PMID: 24744702]
Gadani, S.P.; Smirnov, I.; Smith, A.T.; Overall, C.C.; Kipnis, J. Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury. J. Exp. Med., 2017, 214(2), 285-296.
[] [PMID: 27994070]
Butovsky, O.; Jedrychowski, M.P.; Moore, C.S.; Cialic, R.; Lanser, A.J.; Gabriely, G.; Koeglsperger, T.; Dake, B.; Wu, P.M.; Doykan, C.E.; Fanek, Z.; Liu, L.; Chen, Z.; Rothstein, J.D.; Ransohoff, R.M.; Gygi, S.P.; Antel, J.P.; Weiner, H.L. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci., 2014, 17(1), 131-143.
[] [PMID: 24316888]
Shin, W.H.; Lee, D.Y.; Park, K.W.; Kim, S.U.; Yang, M.S.; Joe, E.H.; Jin, B.K. Microglia expressing interleukin-13 undergo cell death and contribute to neuronal survival in vivo. Glia, 2004, 46(2), 142-152.
[] [PMID: 15042582]
Zhao, X.; Wang, H.; Sun, G.; Zhang, J.; Edwards, N.J.; Aronowski, J. Neuronal interleukin-4 as a modulator of microglial pathways and ischemic brain damage. J. Neurosci., 2015, 35(32), 11281-11291.
[] [PMID: 26269636]
Neumann, H.; Misgeld, T.; Matsumuro, K.; Wekerle, H. Neurotrophins inhibit major histocompatibility class II inducibility of microglia: involvement of the p75 neurotrophin receptor. Proc. Natl. Acad. Sci. USA, 1998, 95(10), 5779-5784.
[] [PMID: 9576961]
Lee, M. Neurotransmitters and microglial-mediated neuroinflammation. Curr. Protein Pept. Sci., 2013, 14(1), 21-32.
[] [PMID: 23441898]
Neumann, H.; Boucraut, J.; Hahnel, C.; Misgeld, T.; Wekerle, H. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur. J. Neurosci., 1996, 8(12), 2582-2590.
[] [PMID: 8996807]
Harrison, J.K.; Jiang, Y.; Chen, S.; Xia, Y.; Maciejewski, D.; McNamara, R.K.; Streit, W.J.; Salafranca, M.N.; Adhikari, S.; Thompson, D.A.; Botti, P.; Bacon, K.B.; Feng, L. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl. Acad. Sci. USA, 1998, 95(18), 10896-10901.
[] [PMID: 9724801]
Cohen, M.; Ben-Yehuda, H.; Porat, Z.; Raposo, C.; Gordon, S.; Schwartz, M. Newly formed endothelial cells regulate myeloid cell activity following spinal cord injury via expression of CD200 ligand. J. Neurosci., 2017, 37(4), 972-985.
[] [PMID: 28123029]
Cronk, J.C.; Derecki, N.C.; Ji, E.; Xu, Y.; Lampano, A.E.; Smirnov, I.; Baker, W.; Norris, G.T.; Marin, I.; Coddington, N.; Wolf, Y.; Turner, S.D.; Aderem, A.; Klibanov, A.L.; Harris, T.H.; Jung, S.; Litvak, V.; Kipnis, J. Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity, 2015, 42(4), 679-691.
[] [PMID: 25902482]
Matcovitch-Natan, O.; Winter, D.R.; Giladi, A.; Vargas Aguilar, S.; Spinrad, A.; Sarrazin, S.; Ben-Yehuda, H.; David, E.; Zelada González, F.; Perrin, P.; Keren-Shaul, H.; Gury, M.; Lara-Astaiso, D.; Thaiss, C.A.; Cohen, M.; Bahar Halpern, K.; Baruch, K.; Deczkowska, A.; Lorenzo-Vivas, E.; Itzkovitz, S.; Elinav, E.; Sieweke, M.H.; Schwartz, M.; Amit, I. Microglia development follows a stepwise program to regulate brain homeostasis. Science, 2016, 353(6301)aad8670
[] [PMID: 27338705]
Nerlov, C.; Graf, T. PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev., 1998, 12(15), 2403-2412.
[] [PMID: 9694804]
Koso, H.; Tsuhako, A.; Lai, C.Y.; Baba, Y.; Otsu, M.; Ueno, K.; Nagasaki, M.; Suzuki, Y.; Watanabe, S. Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina. Glia, 2016, 64(11), 2005-2024.
[] [PMID: 27459098]
Cuevas, V.D.; Anta, L.; Samaniego, R.; Orta-Zavalza, E.; Vladimir de la Rosa, J.; Baujat, G.; Domínguez-Soto, Á.; Sánchez-Mateos, P.; Escribese, M.M.; Castrillo, A.; Cormier-Daire, V.; Vega, M.A.; Corbí, A.L. MAFB determines human macrophage anti-inflammatory polarization: relevance for the pathogenic mechanisms operating in multicentric carpotarsal osteolysis. J. Immunol., 2017, 198(5), 2070-2081.
[] [PMID: 28093525]
Lanzillotta, A.; Porrini, V.; Bellucci, A.; Benarese, M.; Branca, C.; Parrella, E.; Spano, P.F.; Pizzi, M. NF-κB in innate neuroprotection and age-related neurodegenerative diseases. Front. Neurol., 2015, 6, 98.
[] [PMID: 26042083]
Rivas-Arancibia, S.; Zimbrón, L.F.; Rodríguez-Martínez, E.; Maldonado, P.D.; Borgonio Pérez, G.; Sepúlveda-Parada, M. Oxidative stress-dependent changes in immune responses and cell death in the substantia nigra after ozone exposure in rat. Front. Aging Neurosci., 2015, 7, 65.
[] [PMID: 25999851]
Wang, Z.; Liu, D.; Wang, F.; Liu, S.; Zhao, S.; Ling, E.A.; Hao, A. Saturated fatty acids activate microglia via Toll-like receptor 4/NF-κB signalling. Br. J. Nutr., 2012, 107(2), 229-241.
[] [PMID: 21733316]
Kaminska, B.; Mota, M.; Pizzi, M. Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation. Biochim. Biophys. Acta, 2016, 1862(3), 339-351.
[] [PMID: 26524636]
Kierdorf, K.; Erny, D.; Goldmann, T.; Sander, V.; Schulz, C.; Perdiguero, E.G.; Wieghofer, P.; Heinrich, A.; Riemke, P.; Hölscher, C.; Müller, D.N.; Luckow, B.; Brocker, T.; Debowski, K.; Fritz, G.; Opdenakker, G.; Diefenbach, A.; Biber, K.; Heikenwalder, M.; Geissmann, F.; Rosenbauer, F.; Prinz, M. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci., 2013, 16(3), 273-280.
[] [PMID: 23334579]
Masuda, T.; Nishimoto, N.; Tomiyama, D.; Matsuda, T.; Tozaki-Saitoh, H.; Tamura, T.; Kohsaka, S.; Tsuda, M.; Inoue, K. IRF8 is a transcriptional determinant for microglial motility. Purinergic Signal., 2014, 10(3), 515-521.
[] [PMID: 24798612]
Aloi, M.S.; Su, W.; Garden, G.A. The p53 transcriptional network influences microglia behavior and neuroinflammation. Crit. Rev. Immunol., 2015, 35(5), 401-415.
[] [PMID: 26853851]
Abdjul, D.B.; Yamazaki, H.; Kanno, S.I.; Tomizawa, A.; Rotinsulu, H.; Wewengkang, D.S.; Sumilat, D.A.; Ukai, K.; Kapojos, M.M.; Namikoshi, M. An anti-mycobacterial bisfunctionalized sphingolipid and new bromopyrrole alkaloid from the Indonesian marine sponge Agelas sp. J. Nat. Med., 2017, 71(3), 531-536.
[] [PMID: 28364227]
Yu, Z.; Sun, D.; Feng, J.; Tan, W.; Fang, X.; Zhao, M.; Zhao, X.; Pu, Y.; Huang, A.; Xiang, Z.; Cao, L.; He, C. MSX3 switches microglia polarization and protects from inflammation-induced demyelination. J. Neurosci., 2015, 35(16), 6350-6365.
[] [PMID: 25904788]
Saijo, K.; Winner, B.; Carson, C.T.; Collier, J.G.; Boyer, L.; Rosenfeld, M.G.; Gage, F.H.; Glass, C.K.A. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell, 2009, 137(1), 47-59.
[] [PMID: 19345186]
Bruce-Keller, A.J.; Keeling, J.L.; Keller, J.N.; Huang, F.F.; Camondola, S.; Mattson, M.P. Antiinflammatory effects of estrogen on microglial activation. Endocrinology, 2000, 141(10), 3646-3656.
[] [PMID: 11014219]
Yamanaka, M.; Ishikawa, T.; Griep, A.; Axt, D.; Kummer, M.P.; Heneka, M.T. PPARγ/RXRα-induced and CD36-mediated microglial amyloid-β phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J. Neurosci., 2012, 32(48), 17321-17331.
[] [PMID: 23197723]
Savage, J.C.; Jay, T.; Goduni, E.; Quigley, C.; Mariani, M.M.; Malm, T.; Ransohoff, R.M.; Lamb, B.T.; Landreth, G.E. Nuclear receptors license phagocytosis by trem2+ myeloid cells in mouse models of Alzheimer’s disease. J. Neurosci., 2015, 35(16), 6532-6543.
[] [PMID: 25904803]
Parsons, D.W.; Jones, S.; Zhang, X.; Lin, J.C.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Siu, I.M.; Gallia, G.L.; Olivi, A.; McLendon, R.; Rasheed, B.A.; Keir, S.; Nikolskaya, T.; Nikolsky, Y.; Busam, D.A.; Tekleab, H.; Diaz, L.A., Jr; Hartigan, J.; Smith, D.R.; Strausberg, R.L.; Marie, S.K.; Shinjo, S.M.; Yan, H.; Riggins, G.J.; Bigner, D.D.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. An integrated genomic analysis of human glioblastoma multiforme. Science, 2008, 321(5897), 1807-1812.
[] [PMID: 18772396]
Parsons, D.W.; Li, M.; Zhang, X.; Jones, S.; Leary, R.J.; Lin, J.C.; Boca, S.M.; Carter, H.; Samayoa, J.; Bettegowda, C.; Gallia, G.L.; Jallo, G.I.; Binder, Z.A.; Nikolsky, Y.; Hartigan, J.; Smith, D.R.; Gerhard, D.S.; Fults, D.W.; VandenBerg, S.; Berger, M.S.; Marie, S.K.; Shinjo, S.M.; Clara, C.; Phillips, P.C.; Minturn, J.E.; Biegel, J.A.; Judkins, A.R.; Resnick, A.C.; Storm, P.B.; Curran, T.; He, Y.; Rasheed, B.A.; Friedman, H.S.; Keir, S.T.; McLendon, R.; Northcott, P.A.; Taylor, M.D.; Burger, P.C.; Riggins, G.J.; Karchin, R.; Parmigiani, G.; Bigner, D.D.; Yan, H.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. The genetic landscape of the childhood cancer medulloblastoma. Science, 2011, 331(6016), 435-439.
[] [PMID: 21163964]
Bettegowda, C.; Agrawal, N.; Jiao, Y.; Wang, Y.; Wood, L.D.; Rodriguez, F.J.; Hruban, R.H.; Gallia, G.L.; Binder, Z.A.; Riggins, C.J.; Salmasi, V.; Riggins, G.J.; Reitman, Z.J.; Rasheed, A.; Keir, S.; Shinjo, S.; Marie, S.; McLendon, R.; Jallo, G.; Vogelstein, B.; Bigner, D.; Yan, H.; Kinzler, K.W.; Papadopoulos, N. Exomic sequencing of four rare central nervous system tumor types. Oncotarget, 2013, 4(4), 572-583.
[] [PMID: 23592488]
Brennan, C.W.; Verhaak, R.G.; McKenna, A.; Campos, B.; Noushmehr, H.; Salama, S.R.; Zheng, S.; Chakravarty, D.; Sanborn, J.Z.; Berman, S.H.; Beroukhim, R.; Bernard, B.; Wu, C.J.; Genovese, G.; Shmulevich, I.; Barnholtz-Sloan, J.; Zou, L.; Vegesna, R.; Shukla, S.A.; Ciriello, G.; Yung, W.K.; Zhang, W.; Sougnez, C.; Mikkelsen, T.; Aldape, K.; Bigner, D.D.; Van Meir, E.G.; Prados, M.; Sloan, A.; Black, K.L.; Eschbacher, J.; Finocchiaro, G.; Friedman, W.; Andrews, D.W.; Guha, A.; Iacocca, M.; O’Neill, B.P.; Foltz, G.; Myers, J.; Weisenberger, D.J.; Penny, R.; Kucherlapati, R.; Perou, C.M.; Hayes, D.N.; Gibbs, R.; Marra, M.; Mills, G.B.; Lander, E.; Spellman, P.; Wilson, R.; Sander, C.; Weinstein, J.; Meyerson, M.; Gabriel, S.; Laird, P.W.; Haussler, D.; Getz, G.; Chin, L. TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell, 2013, 155(2), 462-477.
[] [PMID: 24120142]
Dubuc, A.M.; Remke, M.; Korshunov, A.; Northcott, P.A.; Zhan, S.H.; Mendez-Lago, M.; Kool, M.; Jones, D.T.; Unterberger, A.; Morrissy, A.S.; Shih, D.; Peacock, J.; Ramaswamy, V.; Rolider, A.; Wang, X.; Witt, H.; Hielscher, T.; Hawkins, C.; Vibhakar, R.; Croul, S.; Rutka, J.T.; Weiss, W.A.; Jones, S.J.; Eberhart, C.G.; Marra, M.A.; Pfister, S.M.; Taylor, M.D. Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma. Acta Neuropathol., 2013, 125(3), 373-384.
[] [PMID: 23184418]
Mack, S.C.; Witt, H.; Piro, R.M.; Gu, L.; Zuyderduyn, S.; Stütz, A.M.; Wang, X.; Gallo, M.; Garzia, L.; Zayne, K.; Zhang, X.; Ramaswamy, V.; Jäger, N.; Jones, D.T.; Sill, M.; Pugh, T.J.; Ryzhova, M.; Wani, K.M.; Shih, D.J.; Head, R.; Remke, M.; Bailey, S.D.; Zichner, T.; Faria, C.C.; Barszczyk, M.; Stark, S.; Seker-Cin, H.; Hutter, S.; Johann, P.; Bender, S.; Hovestadt, V.; Tzaridis, T.; Dubuc, A.M.; Northcott, P.A.; Peacock, J.; Bertrand, K.C.; Agnihotri, S.; Cavalli, F.M.; Clarke, I.; Nethery-Brokx, K.; Creasy, C.L.; Verma, S.K.; Koster, J.; Wu, X.; Yao, Y.; Milde, T.; Sin-Chan, P.; Zuccaro, J.; Lau, L.; Pereira, S.; Castelo-Branco, P.; Hirst, M.; Marra, M.A.; Roberts, S.S.; Fults, D.; Massimi, L.; Cho, Y.J.; Van Meter, T.; Grajkowska, W.; Lach, B.; Kulozik, A.E.; von Deimling, A.; Witt, O.; Scherer, S.W.; Fan, X.; Muraszko, K.M.; Kool, M.; Pomeroy, S.L.; Gupta, N.; Phillips, J.; Huang, A.; Tabori, U.; Hawkins, C.; Malkin, D.; Kongkham, P.N.; Weiss, W.A.; Jabado, N.; Rutka, J.T.; Bouffet, E.; Korbel, J.O.; Lupien, M.; Aldape, K.D.; Bader, G.D.; Eils, R.; Lichter, P.; Dirks, P.B.; Pfister, S.M.; Korshunov, A.; Taylor, M.D. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature, 2014, 506(7489), 445-450.
[] [PMID: 24553142]
Calabrese, C.; Poppleton, H.; Kocak, M.; Hogg, T.L.; Fuller, C.; Hamner, B.; Oh, E.Y.; Gaber, M.W.; Finklestein, D.; Allen, M.; Frank, A.; Bayazitov, I.T.; Zakharenko, S.S.; Gajjar, A.; Davidoff, A.; Gilbertson, R.J. A perivascular niche for brain tumor stem cells. Cancer Cell, 2007, 11(1), 69-82.
[] [PMID: 17222791]
Slongo, M.L.; Molena, B.; Brunati, A.M.; Frasson, M.; Gardiman, M.; Carli, M.; Perilongo, G.; Rosolen, A.; Onisto, M. Functional VEGF and VEGF receptors are expressed in human medulloblastomas. Neuro-oncol., 2007, 9(4), 384-392.
[] [PMID: 17704359]
de Robles, P.; Fiest, K.M.; Frolkis, A.D.; Pringsheim, T.; Atta, C.; St Germaine-Smith, C.; Day, L.; Lam, D.; Jette, N. The worldwide incidence and prevalence of primary brain tumors: a systematic review and meta-analysis. Neuro-oncol., 2015, 17(6), 776-783.
[] [PMID: 25313193]
Arvold, N.D.; Lee, E.Q.; Mehta, M.P.; Margolin, K.; Alexander, B.M.; Lin, N.U.; Anders, C.K.; Soffietti, R.; Camidge, D.R.; Vogelbaum, M.A.; Dunn, I.F.; Wen, P.Y. Updates in the management of brain metastases. Neuro-oncol., 2016, 18(8), 1043-1065.
[] [PMID: 27382120]
Nayak, L.; Lee, E.Q.; Wen, P.Y. Epidemiology of brain metastases. Curr. Oncol. Rep., 2012, 14(1), 48-54.
[] [PMID: 22012633]
Vescovi, A.L.; Galli, R.; Reynolds, B.A. Brain tumour stem cells. Nat. Rev. Cancer, 2006, 6(6), 425-436.
[] [PMID: 16723989]
Park, C.Y.; Tseng, D.; Weissman, I.L. Cancer stem cell-directed therapies: recent data from the laboratory and clinic. Mol. Ther., 2009, 17(2), 219-230.
[] [PMID: 19066601]
Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol., 2016, 131(6), 803-820.
[] [PMID: 27157931]
McFaline-Figueroa, J.R.; Lee, E.Q. Brain Tumors. Am. J. Med., 2018, 131(8), 874-882.
[] [PMID: 29371158]
Cai, X.; Sughrue, M.E. Glioblastoma: new therapeutic strategies to address cellular and genomic complexity. Oncotarget, 2017, 9(10), 9540-9554.
[PMID: 29507709]
Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 2008, 455(7216), 1061-1068.
[] [PMID: 18772890]
Frattini, V.; Trifonov, V.; Chan, J.M.; Castano, A.; Lia, M.; Abate, F.; Keir, S.T.; Ji, A.X.; Zoppoli, P.; Niola, F.; Danussi, C.; Dolgalev, I.; Porrati, P.; Pellegatta, S.; Heguy, A.; Gupta, G.; Pisapia, D.J.; Canoll, P.; Bruce, J.N.; McLendon, R.E.; Yan, H.; Aldape, K.; Finocchiaro, G.; Mikkelsen, T.; Privé, G.G.; Bigner, D.D.; Lasorella, A.; Rabadan, R.; Iavarone, A. The integrated landscape of driver genomic alterations in glioblastoma. Nat. Genet., 2013, 45(10), 1141-1149.
[] [PMID: 23917401]
Wang, J.; Cazzato, E.; Ladewig, E.; Frattini, V.; Rosenbloom, D.I.; Zairis, S.; Abate, F.; Liu, Z.; Elliott, O.; Shin, Y.J.; Lee, J.K.; Lee, I.H.; Park, W.Y.; Eoli, M.; Blumberg, A.J.; Lasorella, A.; Nam, D.H.; Finocchiaro, G.; Iavarone, A.; Rabadan, R. Clonal evolution of glioblastoma under therapy. Nat. Genet., 2016, 48(7), 768-776.
[] [PMID: 27270107]
Verhaak, R.G.; Hoadley, K.A.; Purdom, E.; Wang, V.; Qi, Y.; Wilkerson, M.D.; Miller, C.R.; Ding, L.; Golub, T.; Mesirov, J.P.; Alexe, G.; Lawrence, M.; O’Kelly, M.; Tamayo, P.; Weir, B.A.; Gabriel, S.; Winckler, W.; Gupta, S.; Jakkula, L.; Feiler, H.S.; Hodgson, J.G.; James, C.D.; Sarkaria, J.N.; Brennan, C.; Kahn, A.; Spellman, P.T.; Wilson, R.K.; Speed, T.P.; Gray, J.W.; Meyerson, M.; Getz, G.; Perou, C.M.; Hayes, D.N. Cancer Genome Atlas Research Network. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 2010, 17(1), 98-110.
[] [PMID: 20129251]
Portela, A.; Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol., 2010, 28(10), 1057-1068.
[] [PMID: 20944598]
Mack, S.C.; Hubert, C.G.; Miller, T.E.; Taylor, M.D.; Rich, J.N. An epigenetic gateway to brain tumor cell identity. Nat. Neurosci., 2016, 19(1), 10-19.
[] [PMID: 26713744]
Lee, D.H.; Ryu, H.W.; Won, H.R.; Kwon, S.H. Advances in epigenetic glioblastoma therapy. Oncotarget, 2017, 8(11), 18577-18589.
[] [PMID: 28099914]
Zhang, Y.; Cruickshanks, N.; Pahuski, M.; Yuan, F.; Dutta, A.; Schiff, D.; Purow, B.; Abounader, R. Noncoding RNAs in Glioblastoma.In: Glioblastoma; DeVleeschouwer, S.,Ed.; Brisbane (AU),; , 2017..
[] [PMID: 29251875]
Aldape, K.; Zadeh, G.; Mansouri, S.; Reifenberger, G.; von Deimling, A. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol., 2015, 129(6), 829-848.
[] [PMID: 25943888]
Sanson, M.; Marie, Y.; Paris, S.; Idbaih, A.; Laffaire, J.; Ducray, F.; El Hallani, S.; Boisselier, B.; Mokhtari, K.; Hoang-Xuan, K.; Delattre, J.Y. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J. Clin. Oncol., 2009, 27(25), 4150-4154.
[] [PMID: 19636000]
Ohgaki, H.; Kleihues, P. The definition of primary and secondary glioblastoma. Clin. Cancer Res., 2013, 19(4), 764-772.
[] [PMID: 23209033]
Krengel, U.; Bousquet, P.A. Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front. Immunol., 2014, 5, 325.
[] [PMID: 25101077]
Furukawa, K.; Hamamura, K.; Aixinjueluo, W.; Furukawa, K. Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for cancer therapy. Ann. N. Y. Acad. Sci., 2006, 1086, 185-198.
[] [PMID: 17185516]
Daniotti, J.L.; Vilcaes, A.A.; Torres Demichelis, V.; Ruggiero, F.M.; Rodriguez-Walker, M. Glycosylation of glycolipids in cancer: basis for development of novel therapeutic approaches. Front. Oncol., 2013, 3, 306.
[] [PMID: 24392350]
Berra, B.; Gaini, S.M.; Riboni, L. Correlation between ganglioside distribution and histological grading of human astrocytomas. Int. J. Cancer, 1985, 36(3), 363-366.
[] [PMID: 4030138]
Zeng, G.; Li, D.D.; Gao, L.; Birklé, S.; Bieberich, E.; Tokuda, A.; Yu, R.K. Alteration of ganglioside composition by stable transfection with antisense vectors against GD3-synthase gene expression. Biochemistry, 1999, 38(27), 8762-8769.
[] [PMID: 10393551]
Zeng, G.; Gao, L.; Birklé, S.; Yu, R.K. Suppression of ganglioside GD3 expression in a rat F-11 tumor cell line reduces tumor growth, angiogenesis, and vascular endothelial growth factor production. Cancer Res., 2000, 60(23), 6670-6676.
[PMID: 11118051]
Hettmer, S.; Malott, C.; Woods, W.; Ladisch, S.; Kaucic, K. Biological stratification of human neuroblastoma by complex “B” pathway ganglioside expression. Cancer Res., 2003, 63(21), 7270-7276.
[PMID: 14612523]
Hettmer, S.; Ladisch, S.; Kaucic, K. Low complex ganglioside expression characterizes human neuroblastoma cell lines. Cancer Lett., 2005, 225(1), 141-149.
[] [PMID: 15922866]
Li, C.C.; Eaton, S.A.; Young, P.E.; Lee, M.; Shuttleworth, R.; Humphreys, D.T.; Grau, G.E.; Combes, V.; Bebawy, M.; Gong, J.; Brammah, S.; Buckland, M.E.; Suter, C.M. Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol., 2013, 10(8), 1333-1344.
[] [PMID: 23807490]
Dyatlovitskaya, E.V.; Kandyba, A.G. Role of biologically active sphingolipids in tumor growth. Biochemistry (Mosc.), 2006, 71(1), 10-17.
[] [PMID: 16457613]
Dyatlovitskaya, E.V.; Kandyba, A.G. Sphingolipids in tumor metastases and angiogenesis. Biochemistry (Mosc.), 2006, 71(4), 347-353.
[] [PMID: 16615853]
Birklé, S.; Zeng, G.; Gao, L.; Yu, R.K.; Aubry, J. Role of tumor-associated gangliosides in cancer progression. Biochimie, 2003, 85(3-4), 455-463.
[] [PMID: 12770784]
Caldwell, S.; Heitger, A.; Shen, W.; Liu, Y.; Taylor, B.; Ladisch, S. Mechanisms of ganglioside inhibition of APC function. J. Immunol., 2003, 171(4), 1676-1683.
[] [PMID: 12902465]
Fukumoto, S.; Mutoh, T.; Hasegawa, T.; Miyazaki, H.; Okada, M.; Goto, G.; Furukawa, K.; Urano, T. GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation. J. Biol. Chem., 2000, 275(8), 5832-5838.
[] [PMID: 10681573]
Büll, C.; den Brok, M.H.; Adema, G.J. Sweet escape: sialic acids in tumor immune evasion. Biochim. Biophys. Acta, 2014, 1846(1), 238-246.
[PMID: 25026312]
Seyfried, T.N.; Mukherjee, P. Ganglioside GM3 is antiangiogenic in malignant brain cancer. J. Oncol., 2010, 2010961243
[] [PMID: 20634908]
Mirkin, B.L.; Clark, S.H.; Zhang, C. Inhibition of human neuroblastoma cell proliferation and EGF receptor phosphorylation by gangliosides GM1, GM3, GD1A and GT1B. Cell Prolif., 2002, 35(2), 105-115.
[] [PMID: 11952645]
da Fonseca, A.C.; Amaral, R.; Garcia, C.; Geraldo, L.H.; Matias, D.; Lima, F.R. Microglia in cancer: for good or for bad? Adv. Exp. Med. Biol., 2016, 949, 245-261.
[] [PMID: 27714693]
Roggendorf, W.; Strupp, S.; Paulus, W. Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol., 1996, 92(3), 288-293.
[] [PMID: 8870831]
Ye, X.Z.; Xu, S.L.; Xin, Y.H.; Yu, S.C.; Ping, Y.F.; Chen, L.; Xiao, H.L.; Wang, B.; Yi, L.; Wang, Q.L.; Jiang, X.F.; Yang, L.; Zhang, P.; Qian, C.; Cui, Y.H.; Zhang, X.; Bian, X.W. Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway. J. Immunol., 2012, 189(1), 444-453.
[] [PMID: 22664874]
Matias, D.; Predes, D.; Niemeyer Filho, P.; Lopes, M.C.; Abreu, J.G.; Lima, F.R.S.; Moura Neto, V. Microglia-glioblastoma interactions: New role for Wnt signaling. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(1), 333-340.
[] [PMID: 28554667]
Komohara, Y.; Ohnishi, K.; Kuratsu, J.; Takeya, M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J. Pathol., 2008, 216(1), 15-24.
[] [PMID: 18553315]
Roesch, S.; Rapp, C.; Dettling, S.; Herold-Mende, C. When immune cells turn bad-tumor-associated microglia/macro-phages in glioma. Int. J. Mol. Sci., 2018, 19(2)E436
[] [PMID: 29389898]
Bettinger, I.; Thanos, S.; Paulus, W. Microglia promote glioma migration. Acta Neuropathol., 2002, 103(4), 351-355.
[] [PMID: 11904754]
Brandenburg, S.; Müller, A.; Turkowski, K.; Radev, Y.T.; Rot, S.; Schmidt, C.; Bungert, A.D.; Acker, G.; Schorr, A.; Hippe, A.; Miller, K.; Heppner, F.L.; Homey, B.; Vajkoczy, P. Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors. Acta Neuropathol., 2016, 131(3), 365-378.
[] [PMID: 26718201]
van Echten-Deckert, G.; Walter, J. Sphingolipids: critical players in Alzheimer’s disease. Prog. Lipid Res., 2012, 51(4), 378-393.
[] [PMID: 22835784]
Jana, A.; Hogan, E.L.; Pahan, K. Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death. J. Neurol. Sci., 2009, 278(1-2), 5-15.
[] [PMID: 19147160]
El Alwani, M.; Wu, B.X.; Obeid, L.M.; Hannun, Y.A. Bioactive sphingolipids in the modulation of the inflammatory response. Pharmacol. Ther., 2006, 112(1), 171-183.
[] [PMID: 16759708]
Haughey, N.J. Sphingolipids in neurodegeneration. Neuromolecular Med., 2010, 12(4), 301-305.
[] [PMID: 20737248]
Pyo, H.; Joe, E.; Jung, S.; Lee, S.H.; Jou, I. Gangliosides activate cultured rat brain microglia. J. Biol. Chem., 1999, 274(49), 34584-34589.
[] [PMID: 10574921]
Jou, I.; Lee, J.H.; Park, S.Y.; Yoon, H.J.; Joe, E.H.; Park, E.J. Gangliosides trigger inflammatory responses via TLR4 in brain glia. Am. J. Pathol., 2006, 168(5), 1619-1630.
[] [PMID: 16651628]
Bieberich, E. Ceramide signaling in cancer and stem cells. Future Lipidol., 2008, 3(3), 273-300.
[] [PMID: 19050750]
Wikstrand, C.J.; Fredman, P.; McLendon, R.R.; Svennerholm, L.; Bigner, D.D. Altered expression of ganglioside phenotypes of human gliomas in vivo and in vitro. Mol. Chem. Neuropathol., 1994, 21(2-3), 129-138.
[] [PMID: 7522005]
Wikstrand, C.J.; Fredman, P.; Svennerholm, L.; Bigner, D.D. Detection of glioma-associated gangliosides GM2, GD2, GD3, 3′-isoLM1 3′,6′-isoLD1 in central nervous system tumors in vitro and in vivo using epitope-defined monoclonal antibodies. Prog. Brain Res., 1994, 101, 213-223.
[] [PMID: 7518092]
Yeh, S.C.; Wang, P.Y.; Lou, Y.W.; Khoo, K.H.; Hsiao, M.; Hsu, T.L.; Wong, C.H. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity. Proc. Natl. Acad. Sci. USA, 2016, 113(20), 5592-5597.
[] [PMID: 27143722]
Valentino, L.; Moss, T.; Olson, E.; Wang, H.J.; Elashoff, R.; Ladisch, S. Shed tumor gangliosides and progression of human neuroblastoma. Blood, 1990, 75(7), 1564-1567.
[] [PMID: 2317562]
Potapenko, M.; Shurin, G.V.; de León, J. Gangliosides as immunomodulators. Adv. Exp. Med. Biol., 2007, 601, 195-203.
[] [PMID: 17713006]
McKallip, R.; Li, R.; Ladisch, S. Tumor gangliosides inhibit the tumor-specific immune response. J. Immunol., 1999, 163(7), 3718-3726.
[PMID: 10490967]
Gómez-Nicola, D.; Doncel-Pérez, E.; Nieto-Sampedro, M. Regulation by GD3 of the proinflammatory response of microglia mediated by interleukin-15. J. Neurosci. Res., 2006, 83(5), 754-762.
[] [PMID: 16477650]
Garofalo, S.; Porzia, A.; Mainiero, F.; Di Angelantonio, S.; Cortese, B.; Basilico, B.; Pagani, F.; Cignitti, G.; Chece, G.; Maggio, R.; Tremblay, M.E.; Savage, J.; Bisht, K.; Esposito, V.; Bernardini, G.; Seyfried, T.; Mieczkowski, J.; Stepniak, K.; Kaminska, B.; Santoni, A.; Limatola, C. Environmental stimuli shape microglial plasticity in glioma. eLife, 2017, 6, 6.
[] [PMID: 29286001]
Hannun, Y.A.; Obeid, L.M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol., 2008, 9(2), 139-150.
[] [PMID: 18216770]
Maceyka, M.; Harikumar, K.B.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol., 2012, 22(1), 50-60.
[] [PMID: 22001186]
Anelli, V.; Gault, C.R.; Cheng, A.B.; Obeid, L.M. Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2. J. Biol. Chem., 2008, 283(6), 3365-3375.
[] [PMID: 18055454]
Young, N.; Van Brocklyn, J.R. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp. Cell Res., 2007, 313(8), 1615-1627.
[] [PMID: 17376432]
Nayak, D.; Huo, Y.; Kwang, W.X.; Pushparaj, P.N.; Kumar, S.D.; Ling, E.A.; Dheen, S.T. Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience, 2010, 166(1), 132-144.
[] [PMID: 20036321]
Göggel, R.; Winoto-Morbach, S.; Vielhaber, G.; Imai, Y.; Lindner, K.; Brade, L.; Brade, H.; Ehlers, S.; Slutsky, A.S.; Schütze, S.; Gulbins, E.; Uhlig, S. PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide. Nat. Med., 2004, 10(2), 155-160.
[] [PMID: 14704790]
Masini, E.; Giannini, L.; Nistri, S.; Cinci, L.; Mastroianni, R.; Xu, W.; Comhair, S.A.; Li, D.; Cuzzocrea, S.; Matuschak, G.M.; Salvemini, D. Ceramide: a key signaling molecule in a Guinea pig model of allergic asthmatic response and airway inflammation. J. Pharmacol. Exp. Ther., 2008, 324(2), 548-557.
[] [PMID: 18042827]
Teichgräber, V.; Ulrich, M.; Endlich, N.; Riethmüller, J.; Wilker, B.; De Oliveira-Munding, C.C.; van Heeckeren, A.M.; Barr, M.L.; von Kürthy, G.; Schmid, K.W.; Weller, M.; Tümmler, B.; Lang, F.; Grassme, H.; Döring, G.; Gulbins, E. Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med., 2008, 14(4), 382-391.
[] [PMID: 18376404]
Jung, J.S.; Shin, K.O.; Lee, Y.M.; Shin, J.A.; Park, E.M.; Jeong, J.; Kim, D.H.; Choi, J.W.; Kim, H.S. Anti-inflammatory mechanism of exogenous C2 ceramide in lipopolysaccharide-stimulated microglia. Biochim. Biophys. Acta, 2013, 1831(6), 1016-1026.
[] [PMID: 23384839]
Ghidoni, R.; Caretti, A.; Signorelli, P. Role of sphingolipids in the pathobiology of lung inflammation. Mediators Inflamm., 2015, 2015487508
[] [PMID: 26770018]
Caretti, A.; Torelli, R.; Perdoni, F.; Falleni, M.; Tosi, D.; Zulueta, A.; Casas, J.; Sanguinetti, M.; Ghidoni, R.; Borghi, E.; Signorelli, P. Inhibition of ceramide de novo synthesis by myriocin produces the double effect of reducing pathological inflammation and exerting antifungal activity against A. fumigatus airways infection. Biochim. Biophys. Acta, 2016, 1860(6), 1089-1097.
[] [PMID: 26922830]
Reforgiato, M.R.; Milano, G.; Fabriàs, G.; Casas, J.; Gasco, P.; Paroni, R.; Samaja, M.; Ghidoni, R.; Caretti, A.; Signorelli, P. Inhibition of ceramide de novo synthesis as a postischemic strategy to reduce myocardial reperfusion injury. Basic Res. Cardiol., 2016, 111(2), 12.
[] [PMID: 26786259]
Signorelli, P.; Avagliano, L.; Reforgiato, M.R.; Toppi, N.; Casas, J.; Fabriàs, G.; Marconi, A.M.; Ghidoni, R.; Caretti, A. De novo ceramide synthesis is involved in acute inflammation during labor. Biol. Chem., 2016, 397(2), 147-155.
[] [PMID: 26501163]
Caretti, A.; Vasso, M.; Bonezzi, F.T.; Gallina, A.; Trinchera, M.; Rossi, A.; Adami, R.; Casas, J.; Falleni, M.; Tosi, D.; Bragonzi, A.; Ghidoni, R.; Gelfi, C.; Signorelli, P. Myriocin treatment of CF lung infection and inflammation: complex analyses for enigmatic lipids. Naunyn Schmiedebergs Arch. Pharmacol., 2017, 390(8), 775-790.
[] [PMID: 28439630]
Zulueta, A.; Caretti, A.; Campisi, G.M.; Brizzolari, A.; Abad, J.L.; Paroni, R.; Signorelli, P.; Ghidoni, R. Inhibitors of ceramide de novo biosynthesis rescue damages induced by cigarette smoke in airways epithelia. Naunyn Schmiedebergs Arch. Pharmacol., 2017, 390(7), 753-759.
[] [PMID: 28409208]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy