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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

In Vitro Investigation Demonstrates IGFR/VEGFR Receptor Cross Talk and Potential of Combined Inhibition in Pediatric Central Nervous System Atypical Teratoid Rhabdoid Tumors

Author(s): Halah Obaid, Sunand Kannappan, Mehul Gupta, Yibing Ruan, Chunfen Zhang, Pinaki Bose* and Aru Narendran*

Volume 20, Issue 4, 2020

Page: [295 - 305] Pages: 11

DOI: 10.2174/1568009619666191111153049

Price: $65

Abstract

Background: Atypical teratoid rhabdoid tumor of the central nervous system (CNS ATRT) is a malignancy that commonly affects young children. The biological mechanisms contributing to tumor aggressiveness and resistance to conventional therapies in ATRT are unknown. Previous studies have shown the activity of insulin like growth factor-I receptor (IGF-1R) in ATRT tumor specimens and cell lines. IGF-1R has been shown to cross-talk with other receptor tyrosine kinases (RTKs) in a number of cancer types, leading to enhanced cell proliferation.

Objective: This study aims to evaluate the role of IGF-1 receptor cross-talk in ATRT biology and the potential for therapeutic targeting.

Methods: Cell lines derived from CNS ATRT specimens were analyzed for IGF-1 mediated cell proliferation. A comprehensive receptor tyrosine kinase (RTK) screen was conducted following IGF-1 stimulation. Bioinformatic analysis of publicly available cancer growth inhibition data to identify correlation between IC50 of a VEGFR inhibitor and IGF-1R expression.

Results: Comprehensive RTK screen identified VEGFR-2 cross-activation following IGF-1 stimulation. Bioinformatics analysis demonstrated a positive correlation between IC50 values of VEGFR inhibitor Axitinib and IGF-1R expression, supporting the critical influence of IGF-1R in modulating response to anti-angiogenic therapies.

Conclusion: Overall, our data present a novel experimental framework to evaluate and utilize receptor cross-talk mechanisms to select effective drugs and combinations for future therapeutic trials in ATRT.

Keywords: Crosstalk, ATRT, VEGFR, IGF-1R, drug combination, anti-angiogenic therapies.

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[1]
Richardson, E.A.; Ho, B.; Huang, A. Atypical teratoid rhabdoid tumour: From tumours to therapies. J. Korean Neurosurg. Soc., 2018, 61(3), 302-311.
[http://dx.doi.org/10.3340/jkns.2018.0061] [PMID: 29742888]
[2]
Hilden, J.M.; Meerbaum, S.; Burger, P.; Finlay, J.; Janss, A.; Scheithauer, B.W.; Walter, A.W.; Rorke, L.B.; Biegel, J.A. Central nervous system atypical teratoid/rhabdoid tumor: Results of therapy in children enrolled in a registry. J. Clin. Oncol., 2004, 22(14), 2877-2884.
[http://dx.doi.org/10.1200/JCO.2004.07.073] [PMID: 15254056]
[3]
Biegel, J.A.; Tan, L.; Zhang, F.; Wainwright, L.; Russo, P.; Rorke, L.B. Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin. Cancer Res., 2002, 8(11), 3461-3467.
[PMID: 12429635]
[4]
Narendran, A.; Coppes, L.; Jayanthan, A.; Coppes, M.; Teja, B.; Bernoux, D.; George, D.; Strother, D. Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: A model to elucidate biology and potential targeted therapeutics. J. Neurooncol., 2008, 90(2), 171-180.
[http://dx.doi.org/10.1007/s11060-008-9653-y] [PMID: 18651103]
[5]
Blume-Jensen, P.; Hunter, T. Oncogenic kinase signalling. Nature, 2001, 411(6835), 355-365.
[http://dx.doi.org/10.1038/35077225] [PMID: 11357143]
[6]
Pollak, M. Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer, 2008, 8(12), 915-928.
[http://dx.doi.org/10.1038/nrc2536] [PMID: 19029956]
[7]
Renehan, A.G.; Zwahlen, M.; Minder, C.; O’Dwyer, S.T.; Shalet, S.M.; Egger, M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: Systematic review and meta-regression analysis. Lancet, 2004, 363(9418), 1346-1353.
[http://dx.doi.org/10.1016/S0140-6736(04)16044-3] [PMID: 15110491]
[8]
Playford, M.P.; Bicknell, D.; Bodmer, W.F.; Macaulay, V.M. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc. Natl. Acad. Sci. USA, 2000, 97(22), 12103-12108.
[http://dx.doi.org/10.1073/pnas.210394297] [PMID: 11035789]
[9]
Shen, M.R.; Hsu, Y.M.; Hsu, K.F.; Chen, Y.F.; Tang, M.J.; Chou, C.Y. Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling. Carcinogenesis, 2006, 27(5), 962-971.
[http://dx.doi.org/10.1093/carcin/bgi336] [PMID: 16400188]
[10]
Zhang, D.; Samani, A.A.; Brodt, P. The role of the IGF-I receptor in the regulation of matrix metalloproteinases, tumor invasion and metastasis. Horm. Metab. Res., 2003, 35(11-12), 802-808.
[PMID: 14710361]
[11]
Lee, O.H.; Bae, S.K.; Bae, M.H.; Lee, Y.M.; Moon, E.J.; Cha, H.J.; Kwon, Y.G.; Kim, K.W. Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models. Br. J. Cancer, 2000, 82(2), 385-391.
[http://dx.doi.org/10.1054/bjoc.1999.0931] [PMID: 10646893]
[12]
Economou, M.A.; Andersson, S.; Vasilcanu, D.; All-Ericsson, C.; Menu, E.; Girnita, A.; Girnita, L.; Axelson, M.; Seregard, S.; Larsson, O. Oral picropodophyllin (PPP) is well tolerated in vivo and inhibits IGF-1R expression and growth of uveal melanoma. Invest. Ophthalmol. Vis. Sci., 2008, 49(6), 2337-2342.
[http://dx.doi.org/10.1167/iovs.07-0819] [PMID: 18515579]
[13]
Grulich-Henn, J.; Ritter, J.; Mesewinkel, S.; Heinrich, U.; Bettendorf, M.; Preissner, K.T. Transport of insulin-like growth factor-I across endothelial cell monolayers and its binding to the subendothelial matrix. Exp. Clin. Endocrinol. Diabetes, 2002, 110(2), 67-73.
[http://dx.doi.org/10.1055/s-2002-23488] [PMID: 11928068]
[14]
Treins, C.; Giorgetti-Peraldi, S.; Murdaca, J.; Monthouël-Kartmann, M.N.; Van Obberghen, E. Regulation of hypoxia-inducible factor (HIF)-1 activity and expression of HIF hydroxylases in response to insulin-like growth factor I. Mol. Endocrinol., 2005, 19(5), 1304-1317.
[http://dx.doi.org/10.1210/me.2004-0239] [PMID: 15695372]
[15]
Jayanthan, A.; Bernoux, D.; Bose, P.; Riabowol, K.; Narendran, A. Multi-tyrosine kinase inhibitors in preclinical studies for pediatric CNS AT/RT: Evidence for synergy with topoisomerase-I inhibition. Cancer Cell Int., 2011, 11(1), 44.
[http://dx.doi.org/10.1186/1475-2867-11-44] [PMID: 22206574]
[16]
Chou, T.C. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res., 2010, 70(2), 440-446.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-1947] [PMID: 20068163]
[17]
Rasband, W.S.; Image, J. US National Institutes of Health, Bethesda, Maryland, USA. http://imagej.nih.gov/ij/
[18]
Rahimi, N.; Kazlauskas, A. A role for cadherin-5 in regulation of vascular endothelial growth factor receptor 2 activity in endothelial cells. Mol. Biol. Cell, 1999, 10(10), 3401-3407.
[http://dx.doi.org/10.1091/mbc.10.10.3401] [PMID: 10512875]
[19]
Rhodes, D.R.; Yu, J.; Shanker, K.; Deshpande, N.; Varambally, R.; Ghosh, D.; Barrette, T.; Pandey, A.; Chinnaiyan, A.M. ONCOMINE: A cancer microarray database and integrated data-mining platform. Neoplasia, 2004, 6(1), 1-6.
[http://dx.doi.org/10.1016/S1476-5586(04)80047-2] [PMID: 15068665]
[20]
Yang, W.; Soares, J.; Greninger, P.; Edelman, E.J.; Lightfoot, H.; Forbes, S.; Bindal, N.; Beare, D.; Smith, J.A.; Thompson, I.R.; Ramaswamy, S. Genomics of drug sensitivity in cancer (GDSC): A resource for biomarker discovery in cancer cells. Eur. J. Cancer, 2016, 69, S82.
[http://dx.doi.org/10.1016/S0959-8049(16)32839-8]
[21]
Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer, 2003, 3(10), 721-732.
[http://dx.doi.org/10.1038/nrc1187] [PMID: 13130303]
[22]
Hirsilä, M.; Koivunen, P.; Xu, L.; Seeley, T.; Kivirikko, K.I.; Myllyharju, J. Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway. FASEB J., 2005, 19(10), 1308-1310.
[http://dx.doi.org/10.1096/fj.04-3399fje] [PMID: 15941769]
[23]
LeRoith, D.; Roberts, C.T., Jr The insulin-like growth factor system and cancer. Cancer Lett., 2003, 195(2), 127-137.
[http://dx.doi.org/10.1016/S0304-3835(03)00159-9] [PMID: 12767520]
[24]
Ogino, S.; Cohen, M.L.; Abdul-Karim, F.W. Atypical teratoid/rhabdoid tumor of the CNS: Cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin D, and Ki-67. Mod. Pathol., 1999, 12(4), 379-385.
[PMID: 10229502]
[25]
Jin, Q.; Esteva, F.J. Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J. Mammary Gland Biol. Neoplasia, 2008, 13(4), 485-498.
[http://dx.doi.org/10.1007/s10911-008-9107-3] [PMID: 19034632]
[26]
D’cunja, J.; Shalaby, T.; Rivera, P.; von Büren, A.; Patti, R.; Heppner, F.L.; Arcaro, A.; Rorke-Adams, L.B.; Phillips, P.C.; Grotzer, M.A. Antisense treatment of IGF-IR induces apoptosis and enhances chemosensitivity in central nervous system atypical teratoid/rhabdoid tumours cells. Eur. J. Cancer, 2007, 43(10), 1581-1589.
[http://dx.doi.org/10.1016/j.ejca.2007.03.003] [PMID: 17446062]
[27]
Arcaro, A.; Doepfner, K.T.; Boller, D.; Guerreiro, A.S.; Shalaby, T.; Jackson, S.P.; Schoenwaelder, S.M.; Delattre, O.; Grotzer, M.A. and; Fischer, B. Novel role for insulin as an autocrine growth factor for malignant brain tumour cells. Biochem. J., 2007, 406(1), 57-66.
[http://dx.doi.org/10.1042/BJ20070309] [PMID: 17506723]
[28]
Punglia, R.S.; Lu, M.; Hsu, J.; Kuroki, M.; Tolentino, M.J.; Keough, K.; Levy, A.P.; Levy, N.S.; Goldberg, M.A.; D’Amato, R.J.; Adamis, A.P. Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. Diabetes, 1997, 46(10), 1619-1626.
[http://dx.doi.org/10.2337/diacare.46.10.1619] [PMID: 9313759]
[29]
Fukuda, R.; Hirota, K.; Fan, F.; Jung, Y.D.; Ellis, L.M.; Semenza, G.L. Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J. Biol. Chem., 2002, 277(41), 38205-38211.
[http://dx.doi.org/10.1074/jbc.M203781200] [PMID: 12149254]
[30]
Bermont, L.; Lamielle, F.; Lorchel, F. Insulin up-regulates vascular endothelial growth factor and stabilizes its messengers in endometrial adenocarcinoma cells. J. Clin. Endocrinol. Metab., 2001, 86(1), 363-368.
[http://dx.doi.org/10.1210/jc.86.1.363] [PMID: 11232025]
[31]
Gruden, G.; Araf, S.; Zonca, S.; Burt, D.; Thomas, S.; Gnudi, L. and; Viberti, G. IGF-I induces vascular endothelial growth factor in human mesangial cells via a Src-dependent mechanism. Kidney Int., 2003, 63(4), 1249-1255.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00857.x] [PMID: 12631341]
[32]
Mitsiades, N.; McMullan, C.J.; Poulaki, V.; Shringarpure, R.; Libermann, T.A.; Hideshima, T.; Chauhan, D.; Schlossman, R.L.; Richardson, P.G.; Munshi, N.C.; Garcia-Echeverria, C. NVP-AEW541: A selective small molecule IGF-1R tyrosine kinase inhibitor is active against multiple myeloma and other hematologic neoplasias and solid tumors. Blood, 2004, 104(11), 766-786.
[http://dx.doi.org/10.1182/blood.V104.11.766.766]
[33]
Moser, C.; Schachtschneider, P.; Lang, S.A.; Gaumann, A.; Mori, A.; Zimmermann, J.; Schlitt, H.J.; Geissler, E.K.; Stoeltzing, O. Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. Eur. J. Cancer, 2008, 44(11), 1577-1586.
[http://dx.doi.org/10.1016/j.ejca.2008.04.003] [PMID: 18445520]
[34]
Catrina, S.B.; Botusan, I.R.; Rantanen, A. Hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha are expressed in kaposi sarcoma and modulated by insulin-like growth factor-I. Clin. Cancer Res., 2006, 12(15), 4506-4514.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2473] [PMID: 16899596]
[35]
Perrot-Applanat, M.; Di Benedetto, M. Autocrine functions of VEGF in breast tumor cells: Adhesion, survival, migration and invasion. Cell Adhes. Migr., 2012, 6(6), 547-553.
[http://dx.doi.org/10.4161/cam.23332] [PMID: 23257828]

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