Implication of Prophetic Variables and their Impulsive Interplay in CA Prostate Patients Experiencing Osteo-Metastasis

Author(s): Muhammad A.B. Ashraf, Ayesha Zahid, Shazia Ashraf, Sulayman Waquar, Saima Iqbal, Arif Malik*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 17 , 2020

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Graphical Abstract:


Aims: To identify variables having a critical role in prostate cancer patients experiencing osteometastasis.

Background: Prostatic carcinoma is a multifactorial complex disorder that exhibits an increased propensity to develop bone metastasis. An interplay of inflammatory and bone remodeling parameters promotes the formation of pre-metastatic niches in bones of patients, which could render them more vulnerable to skeletal disabilities.

Objective: To evaluate the multi-dynamic inter-relationship of circulating variables in prostate cancer patients experiencing osteo-metastasis.

Materials and Methods: Fifty-seven (n=57) men with clinically confirmed prostate cancer, fifty-nine (n=59) with skeletal metastases, and one hundred (n=100) healthy subjects i.e., men aging from 53-84 years with no clinical evidence of prostate were recruited from the Jinnah Hospital Lahore, Pakistan. Informed consent was obtained, and a venous blood sample was drawn and stored at -70oC until assayed. Levels of variables were evaluated using appropriate methods. Levels of Matrix Metalloproteinases (MMPs), Osteopontin (OPN), TGH- β, and sRANKL were estimated by the ELISA method. Each sample was suspended and the given protocol was employed. ELISA readings were obtained for the estimation of all variables.

Results: Highly significant (P˂0.05) differential expression of oxidative stress, inflammatory cytokines, and bone remodeling variables were observed in localized and osteo-metastatic CA prostate patients. A strong positive correlation was revealed among OPN, sRANKL, MMP-7, MMP-9, PSA, and TGF-β (OPN vs. MMP-7, r=0.698* and OPN vs. MMP-9, r=0.765**, OPN vs. RANKL, =0.856*, sRANKL vs. MMP-9, r=0.825**, TGF- β vs. RANKL, r=0.868* and PSA vs. TGF- β, r=0.752*); lower levels of OPG were estimated in metastasized patients, showing that both osteolytic and osteoblastic phases of bone remodeling occur simultaneously.

Conclusion: The altered oxidative and inflammatory responses endorse Matrix Metalloproteinases (MMPs) increased activity, RANKL/OPG imbalance, and enhanced bone matrix proteins turnover, which can foster the process of osteo-metastasis. The perturbed RANKL/OPG drift and enhanced PSA levels are associated with increased TGF-β activity to aggravate Epithelial Mesenchymal transition (EM) and osteo-tropism of prostate cancer. Thus, designing novel targets of these major variables can minimize the incidence of prostate cancer patients.

Keywords: Prostate specific antigen, osteopontin, osteoprotegrin, transforming growth factor-beta, prostate cancer, MMP.

Cornford, P.; Bellmunt, J.; Bolla, M.; Briers, E.; De Santis, M.; Gross, T.; Henry, A.M.; Joniau, S.; Lam, T.B.; Mason, M.D.; van der Poel, H.G.; van der Kwast, T.H.; Rouvière, O.; Wiegel, T.; Mottet, N. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: Treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur. Urol., 2017, 71(4), 630-642.
[] [PMID: 27591931]
Hensel, J.; Thalmann, G.N. Biology of bone metastases in prostate cancer. Urology, 2016, 92, 6-13.
[] [PMID: 26768714]
Dy, G.W.; Gore, J.L.; Forouzanfar, M.H.; Naghavi, M.; Fitzmaurice, C. Global burden of urologic cancers, 1990-2013. Eur. Urol., 2017, 71(3), 437-446.
[] [PMID: 28029399]
Manna, F.; Karkampouna, S.; Zoni, E.; De Menna, M.; Hensel, J.; Thalmann, G.N.; Kruithof-de Julio, M. Metastases in prostate cancer. Cold Spring Harb. Perspect. Med., 2019, 9(3)a033688
[] [PMID: 29661810]
Sartor, O.; Flood, E.; Beusterien, K.; Park, J.; Webb, I.; MacLean, D.; Wong, B.J.; Mark Lin, H. Health-related quality of life in advanced prostate cancer and its treatments: Biochemical failure and metastatic disease populations. Clin. Genitourin. Cancer, 2015, 13(2), 101-112.
[] [PMID: 25262852]
Iranikhah, M.; Stricker, S.; Freeman, M.K. Future of bisphosphonates and denosumab for men with advanced prostate cancer. Cancer Manag. Res., 2014, 6, 217-224.
[] [PMID: 24833918]
von Moos, R.; Body, J.J.; Egerdie, B.; Stopeck, A.; Brown, J.; Fallowfield, L.; Patrick, D.L.; Cleeland, C.; Damyanov, D.; Palazzo, F.S.; Marx, G.; Zhou, Y.; Braun, A.; Balakumaran, A.; Qian, Y. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases. Support. Care Cancer, 2016, 24(3), 1327-1337.
[] [PMID: 26329397]
Harada, M.; Iida, M.I.; Yamaguchi, M.; Shida, K. Analysis of bone metastasis of prostatic adenocarcinoma in 137 autopsy cases. In:Prostate Cancer and Bone Metastasis; Springer: Boston, MA, 1992, pp. 173-182.
Decker, A.M.; Jung, Y.; Cackowski, F.; Taichman, R.S. The role of hematopoietic stem cell niche in prostate cancer bone metastasis. J. Bone Oncol., 2016, 5(3), 117-120.
[] [PMID: 27761370]
Vignani, F.; Bertaglia, V.; Buttigliero, C.; Tucci, M.; Scagliotti, G.V.; Di Maio, M. Skeletal metastases and impact of anticancer and bone-targeted agents in patients with castration-resistant prostate cancer. Cancer Treat. Rev., 2016, 44, 61-73.
[] [PMID: 26907461]
Heidenreich, A.; Bastian, P.J.; Bellmunt, J.; Bolla, M.; Joniau, S.; van der Kwast, T.; Mason, M.; Matveev, V.; Wiegel, T.; Zattoni, F.; Mottet, N. European Association of Urology. EAU guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent-update 2013. Eur. Urol., 2014, 65(1), 124-137.
[] [PMID: 24207135]
Parker, C.; Gillessen, S.; Heidenreich, A.; Horwich, A. ESMO Guidelines Committee. Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2015, 26(5)(Suppl. 5), v69-v77.
[] [PMID: 26205393]
Gartrell, B.A.; Saad, F. Managing bone metastases and reducing skeletal related events in prostate cancer. Nat. Rev. Clin. Oncol., 2014, 11(6), 335-345.
[] [PMID: 24821212]
Poulsen, M.H.; Frost, M.; Abrahamsen, B.; Gerke, O.; Walter, S.; Lund, L. Osteoporosis and prostate cancer; a 24-month prospective observational study during androgen deprivation therapy. Scand. J. Urol., 2019, 53(1), 34-39.
[] [PMID: 30777478]
Mani, R.S.; Amin, M.A.; Li, X.; Kalyana-Sundaram, S.; Veeneman, B.A.; Wang, L.; Ghosh, A.; Aslam, A.; Ramanand, S.G.; Rabquer, B.J.; Kimura, W.; Tran, M.; Cao, X.; Roychowdhury, S.; Dhanasekaran, S.M.; Palanisamy, N.; Sadek, H.A.; Kapur, P.; Koch, A.E.; Chinnaiyan, A.M. Inflammation-induced oxidative stress mediates gene fusion formation in prostate cancer. Cell Rep., 2016, 17(10), 2620-2631.
[] [PMID: 27926866]
Anuja, K.; Roy, S.; Ghosh, C.; Gupta, P.; Bhattacharjee, S.; Banerjee, B. Prolonged inflammatory microenvironment is crucial for pro-neoplastic growth and genome instability: A detailed review. Inflamm. Res., 2017, 66(2), 119-128.
[] [PMID: 27653961]
Sabharwal, S.S.; Schumacker, P.T. Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles’ heel? Nat. Rev. Cancer, 2014, 14(11), 709-721.
[] [PMID: 25342630]
Raza, M.H.; Siraj, S.; Arshad, A.; Waheed, U.; Aldakheel, F.; Alduraywish, S.; Arshad, M. ROS-modulated therapeutic approaches in cancer treatment. J. Cancer Res. Clin. Oncol., 2017, 143(9), 1789-1809.
[] [PMID: 28647857]
Luo, C.; Li, Y.; Wang, H.; Cui, Y.; Feng, Z.; Li, H.; Li, Y.; Wang, Y.; Wurtz, K.; Weber, P.; Long, J.; Liu, J. Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells. Curr. Cancer Drug Targets, 2013, 13(6), 625-639.
[] [PMID: 23597197]
Kirschenbaum, A.; Izadmehr, S.; Yao, S.; O’Connor-Chapman, K.L.; Huang, A.; Gregoriades, E.M.; Yakar, S.; Levine, A.C. Prostatic acid phosphatase alters the RANKL/OPG system and induces osteoblastic prostate cancer bone metastases. Endocrinology, 2016, 157(12), 4526-4533.
[] [PMID: 27783536]
Martin, T.J.; Johnson, R.W. Multiple actions of PTHrP in breast cancer bone metastasis. Br. J. Pharmacol., 2019, 14(2), 307.
Sisay, M.; Mengistu, G.; Edessa, D. The RANK/RANKL/OPG system in tumorigenesis and metastasis of cancer stem cell: Potential targets for anticancer therapy. OncoTargets Ther., 2017, 10, 3801-3810.
[] [PMID: 28794644]
Zhang, Q.; Helfand, B.T.; Carneiro, B.A.; Qin, W.; Yang, X.J.; Lee, C.; Zhang, W.; Giles, F.J.; Cristofanilli, M.; Kuzel, T.M. Efficacy against human prostate cancer by prostate-specific membrane antigen-specific, transforming growth factor-β insensitive genetically targeted CD8+ T-cells derived from patients with metastatic castrate-resistant disease. Eur. Urol., 2018, 73(5), 648-652.
[] [PMID: 29275833]
Chen, Y.C.; Sosnoski, D.M.; Mastro, A.M. Breast cancer metastasis to the bone: mechanisms of bone loss. Breast Cancer Res., 2010, 12(6), 215.
[] [PMID: 21176175]
Karlsson, T.; Sundar, R.; Widmark, A.; Landström, M.; Persson, E. Osteoblast-derived factors promote metastatic potential in human prostate cancer cells, in part via non-canonical transforming growth factor β (TGFβ) signaling. Prostate, 2018, 78(6), 446-456.
[] [PMID: 29383751]
Chiechi, A.; Guise, T.A. Pathobiology of osteolytic and osteoblastic bone metastases. In:Metastatic Bone Disease; Springer: New York, NY, 2016, pp. 15-35.
Anunobi, C.C.; Koli, K.; Saxena, G.; Banjo, A.A.; Ogbureke, K.U. Expression of the SIBLINGs and their MMP partners in human benign and malignant prostate neoplasms. Oncotarget, 2016, 7(30), 48038-48049.
[] [PMID: 27331624]
Huang, W.C.; Xie, Z.; Konaka, H.; Sodek, J.; Zhau, H.E.; Chung, L.W. Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: Role of cAMP-dependent protein kinase A signaling pathway. Cancer Res., 2005, 65(6), 2303-2313.
[] [PMID: 15781644]
Shokoohmand, A.; Ren, J.; Baldwin, J.; Atack, A.; Shafiee, A.; Theodoropoulos, C.; Wille, M.L.; Tran, P.A.; Bray, L.J.; Smith, D.; Chetty, N.; Pollock, P.M.; Hutmacher, D.W.; Clements, J.A.; Williams, E.D.; Bock, N. Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts. Biomaterials, 2019, 220119402
[] [PMID: 31400612]
Armstrong, A.J.; Gupta, S.; Healy, P.; Kemeny, G.; Leith, L.B.; Zalutsky, M.; Spritzer, C.; Davies, C.; Ware, K.; Somarelli, J.; Wood, K. Genomic and phenotypic evidence for prostate cancer osteomimicry in circulating tumor cells from men with metastatic Castration Resistant Prostate Cancer (mCRPC) treated with radium-223. J. Clin. Oncol., 2018, 36(6), 160-160.
Prieto-García, E.; Díaz-García, C.V.; García-Ruiz, I.; Agulló-Ortuño, M.T. Epithelial-to-mesenchymal transition in tumor progression. Med. Oncol., 2017, 34(7), 122.
[] [PMID: 28560682]
Begemann, D.; Anastos, H.; Kyprianou, N. Cell death under epithelial-mesenchymal transition control in prostate cancer therapeutic response. Int. J. Urol., 2018, 25(4), 318-326.
[] [PMID: 29345000]
Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(2), 69-84.
[] [PMID: 30459476]
Drivalos, A.; Papatsoris, A.G.; Chrisofos, M.; Efstathiou, E.; Dimopoulos, M.A. The role of the cell adhesion molecules (integrins/cadherins) in prostate cancer. Int. Braz J Urol, 2011, 37(3), 302-306.
[] [PMID: 21756376]
Desgrosellier, J.S.; Cheresh, D.A. Integrins in cancer: Biological implications and therapeutic opportunities. Nat. Rev. Cancer, 2010, 10(1), 9-22.
[] [PMID: 20029421]
Manca, P.; Pantano, F.; Iuliani, M.; Ribelli, G.; De Lisi, D.; Danesi, R.; Del Re, M.; Vincenzi, B.; Tonini, G.; Santini, D. Determinants of bone specific metastasis in prostate cancer. Crit. Rev. Oncol. Hematol., 2017, 112, 59-66.
[] [PMID: 28325265]
Liu, B.; Xu, M.; Guo, Z.; Liu, J.; Chu, X.; Jiang, H. Interleukin-8 promotes prostate cancer bone metastasis through upregulation of bone sialoprotein. Oncol. Lett., 2019, 17(5), 4607-4613.
[] [PMID: 30988819]
Kakkar, P.; Das, B.; Visvanathan, P.N. A modified spectrophotometric assay of superoxide dismutase. Indian J. Biochem., 1972, 197, 588-590.
Moron, M.S.; Depierre, J.W.; Mannervik, B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim. Biophys. Acta, 1979, 582(1), 67-78.
[] [PMID: 760819]
Aebi, H. Catalase. In:Methods of Enzymatic Analysis; Academic press: USA, 1974, pp. 673-684.
David, M.; Richard, J.S. Horn, H.D. Glutathione reductase. Om: Methods of Enzymatic Analysis; Academic Press: USA, 1965, pp. 875-879.
Kumar, B.; Koul, S.; Khandrika, L.; Meacham, R.B.; Koul, H.K. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res., 2008, 68(6), 1777-1785.
[] [PMID: 18339858]
Li, L.; Fath, M.A.; Scarbrough, P.M.; Watson, W.H.; Spitz, D.R. Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer. Redox Biol., 2015, 4, 127-135.
[] [PMID: 25560241]
Shibata, T.; Ohta, T.; Tong, K.I.; Kokubu, A.; Odogawa, R.; Tsuta, K.; Asamura, H.; Yamamoto, M.; Hirohashi, S. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl. Acad. Sci. USA, 2008, 105(36), 13568-13573.
[] [PMID: 18757741]
Hayes, J.D.; Dinkova-Kostova, A.T. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem. Sci., 2014, 39(4), 199-218.
[] [PMID: 24647116]
Singh, A.; Happel, C.; Manna, S.K.; Acquaah-Mensah, G.; Carrerero, J.; Kumar, S.; Nasipuri, P.; Krausz, K.W.; Wakabayashi, N.; Dewi, R.; Boros, L.G.; Gonzalez, F.J.; Gabrielson, E.; Wong, K.K.; Girnun, G.; Biswal, S. Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. J. Clin. Invest., 2013, 123(7), 2921-2934.
[] [PMID: 23921124]
Tome, M.E.; Johnson, D.B.; Samulitis, B.K.; Dorr, R.T.; Briehl, M.M. Glucose 6-phosphate dehydrogenase overexpression models glucose deprivation and sensitizes lymphoma cells to apoptosis. Antioxid. Redox Signal., 2006, 8(7-8), 1315-1327.
[] [PMID: 16910779]
Mohsenzadegan, M.; Seif, F.; Farajollahi, M.M.; Khoshmirsafa, M. Anti-oxidants as chemopreventive agents in prostate cancer, A gap between preclinical and clinical studies. Rec. Pat. Anticancer Drug Discov., 2018, 13(2), 224-239.
[] [PMID: 29446748]
Prasad, S.; Gupta, S.C.; Tyagi, A.K. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer Lett., 2017, 387, 95-105.
[] [PMID: 27037062]
Seo, K.H.; Ryu, H.W.; Park, M.J.; Park, K.H.; Kim, J.H.; Lee, M.J.; Kang, H.J.; Kim, S.L.; Lee, J.H.; Seo, W.D.; Mangosenone, F. A furanoxanthone from Garcianamangostana, induces reactive oxygen species-mediated apoptosis in lung cancer cells and decreases xenograft tumour growth. Phytother. Res., 2015, 29(11), 1753-1760.
[] [PMID: 26310849]
Yang, J.B.; Khan, M.; He, Y.Y.; Yao, M.; Li, Y.M.; Gao, H.W.; Ma, T.H. Tubeimoside-1 induces oxidative stress-mediated apoptosis and G0/G1 phase arrest in human prostate carcinoma cells in vitro. Acta Pharmacol. Sin., 2016, 37(7), 950-962.
[] [PMID: 27292614]
Yu, J.S.; Kim, A.K. Platycodin D induces reactive oxygen species-mediated apoptosis signal-regulating kinase 1 activation and endoplasmic reticulum stress response in human breast cancer cells. J. Med. Food, 2012, 15(8), 691-699.
[] [PMID: 22784044]
Chen, W.J.; Yu, C.; Yang, Z.; He, J.L.; Yin, J.; Liu, H.Z.; Liu, H.T.; Wang, Y.X. Tubeimoside-1 induces G2/M phase arrest and apoptosis in SKOV-3 cells through increase of intracellular Ca2+ and caspase-dependent signaling pathways. Int. J. Oncol., 2012, 40(2), 535-543.
[PMID: 21971569]
Granados-Principal, S.; Quiles, J.L.; Ramirez-Tortosa, C.L.; Sanchez-Rovira, P.; Ramirez-Tortosa, M.C. New advances in molecular mechanisms and the prevention of adriamycin toxicity by antioxidant nutrients. Food Chem. Toxicol., 2010, 48(6), 1425-1438.
[] [PMID: 20385199]
Zhang, S.; Liu, X.; Bawa-Khalfe, T.; Lu, L.S.; Lyu, Y.L.; Liu, L.F.; Yeh, E.T. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med., 2012, 18(11), 1639-1642.
[] [PMID: 23104132]
Kryston, T.B.; Georgiev, A.B.; Pissis, P.; Georgakilas, A.G. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat. Res., 2011, 711(1-2), 193-201.
[] [PMID: 21216256]
Draffin, J.E.; McFarlane, S.; Hill, A.; Johnston, P.G.; Waugh, D.J. CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res., 2004, 64(16), 5702-5711.
[] [PMID: 15313910]
Jin, C.H.; Miyaura, C.; Ishimi, Y.; Hong, M.H.; Sato, T.; Abe, E.; Suda, T. Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts. Mol. Cell. Endocrinol., 1990, 74(3), 221-228.
[] [PMID: 2095355]
Pang, X.; Gong, K.; Zhang, X.; Wu, S.; Cui, Y.; Qian, B.Z. Osteopontin as a multifaceted driver of bone metastasis and drug resistance. Pharmacol. Res., 2019, 144, 235-244.
[] [PMID: 31028902]
Desai, B.; Rogers, M.J.; Chellaiah, M.A. Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells. Mol. Cancer, 2007, 6(1), 18.
[] [PMID: 17343740]
Robertson, B.W.; Chellaiah, M.A. Osteopontin induces β-catenin signaling through activation of Akt in prostate cancer cells. Exp. Cell Res., 2010, 316(1), 1-11.
[] [PMID: 19850036]
Rucci, N.; Teti, A. Osteomimicry: How the seed grows in the soil. Calcif. Tissue Int., 2018, 102(2), 131-140.
[] [PMID: 29147721]
Karadag, A.; Ogbureke, K.U.; Fedarko, N.S.; Fisher, L.W. Bone sialoprotein, matrix metalloproteinase 2, and α(v)β3 integrin in osteotropic cancer cell invasion. J. Natl. Cancer Inst., 2004, 96(12), 956-965.
[] [PMID: 15199115]
Fedarko, N.S.; Fohr, B.; Robey, P.G.; Young, M.F.; Fisher, L.W. Factor H binding to bone sialoprotein and osteopontin enables tumor cell evasion of complement-mediated attack. J. Biol. Chem., 2000, 275(22), 16666-16672.
[] [PMID: 10747989]
Bellahcène, A.; Castronovo, V.; Ogbureke, K.U.; Fisher, L.W.; Fedarko, N.S. Small Integrin-Binding Ligand N-linked Glycoproteins (SIBLINGs): Multifunctional proteins in cancer. Nat. Rev. Cancer, 2008, 8(3), 212-226.
[] [PMID: 18292776]
Xu, M.; Jiang, H.; Wang, H.; Liu, J.; Liu, B.; Guo, Z. SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP2. Oncol. Rep., 2018, 40(2), 726-736.
[] [PMID: 29917166]
Chakraborty, G.; Jain, S.; Kundu, G.C. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res., 2008, 68(1), 152-161.
[] [PMID: 18172307]
Kale, S.; Raja, R.; Thorat, D.; Soundararajan, G.; Patil, T.V.; Kundu, G.C. Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via α9β1 integrin. Oncogene, 2014, 33(18), 2295-2306.
[] [PMID: 23728342]
Sturge, J.; Caley, M.P.; Waxman, J. Bone metastasis in prostate cancer: emerging therapeutic strategies. Nat. Rev. Clin. Oncol., 2011, 8(6), 357-368.
[] [PMID: 21556025]
Christoph, F.; König, F.; Lebentrau, S.; Jandrig, B.; Krause, H.; Strenziok, R.; Schostak, M. RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary and metastatic prostate cancer disease. World J. Urol., 2018, 36(2), 187-192.
[] [PMID: 29204705]
Zelivianski, S.; Glowacki, R.; Lin, M.F. Transcriptional activation of the human prostatic acid phosphatase gene by NF-kappaB via a novel hexanucleotide-binding site. Nucleic Acids Res., 2004, 32(12), 3566-3580.
[] [PMID: 15240830]
Siampanopoulou, M.; El, M.; Moustakas, G.; Haritanti, A.; Gotzamani-Psarrakou, A. The role of serum osteoprotegerine in metastatic prostate cancer - a case control study. Hippokratia, 2016, 20(2), 133-138.
[PMID: 28416910]
Karamanolakis, D.; Armakolas, A.; Koutsilieris, M. Castration-resistant prostate cancer: The targeting of bone microenvironment-related survival factors for prostate cancer cells. Clin. Cancer Drugs, 2016, 3(1), 16-22.
Guise, T.A.; Mundy, G.R. Cancer and bone. Endocr. Rev., 1998, 19(1), 18-54.
[PMID: 9494779]
Fournier, P.G.; Dunn, L.K.; Clines, G.A.; Guise, T.A. Tumor-bone cell interactions in bone metastases. In:Bone Cancer; Academic Press: USA, 2010, pp. 9-40.
Yin, J.J.; Pollock, C.B.; Kelly, K. Mechanisms of cancer metastasis to the bone. Cell Res., 2005, 15(1), 57-62.
[] [PMID: 15686629]
Nadiminty, N.; Lou, W.; Lee, S.O.; Mehraein-Ghomi, F.; Kirk, J.S.; Conroy, J.M.; Zhang, H.; Gao, A.C. Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. Clin. Cancer Res., 2006, 12(5), 1420-1430.
[] [PMID: 16533764]
Dallas, S.L.; Zhao, S.; Cramer, S.D.; Chen, Z.; Peehl, D.M.; Bonewald, L.F. Preferential production of latent transforming growth factor β-2 by primary prostatic epithelial cells and its activation by prostate-specific antigen. J. Cell. Physiol., 2005, 202(2), 361-370.
[] [PMID: 15389580]

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Year: 2020
Page: [2106 - 2113]
Pages: 8
DOI: 10.2174/1871520620666200727094430
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