Role of Vascular Endothelial Growth Factor and Transforming Growth Factor-β in Hepatocellular Carcinoma

Year 2017, , 25 - 31, 01.04.2017

Saurabh Kumar Chhonker Divya Rawat Raj Kumar Koiri

https://doi.org/10.5455/umj.20170608022309

Abstract

Hepatocellular carcinoma is one of the most common malignant tumor and leading cause of death worldwide. Tumor genes, signals from tumor stroma, recruited inflammatory cells and hypoxia has been reported to switch on angiogenesis. Vascular endothelial growth factor is a pleiotropic factor that regulates cell proliferation, vascular permeability and plays an important role in tumor angiogenesis through its different angiogenic receptors. Multifunctional regulatory cytokine transforming growth factor-β also controls cell proliferation, differentiation, extracellular matrix production and survival/or apoptosis of many types cells. By raising level of epithelial–mesenchymal transition, transforming growth factor-β creates a favourable microenvironment for tumor cell growth. Depending upon the stage of cancer progression it can either initiate tumor development, progression and metastasis or can act as a tumor suppressor. In the present review, an attempt has been made to comprehensively define the role of Vascular Endothelial Growth Factor and transforming growth factor-β in the development and progression of hepatocellular carcinoma.

Keywords

Hepatocellular carcinoma, VEGF, TGF-β, angiogenesis, cancer

References

• Simbaqueba Ferlay J, Shin HR, Bray Forman FD, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int J Cancer 2010;127: 2893– 2917.
• Mulcahy MF. Management of hepatocellular cancer. Curr Treat Options Oncol 2005;6: 423–435.
• Thomas MB, Abbruzzese JL. Opportunities for targeted therapies in hepatocellular carcinoma. J Clin Oncol 2005;23: 8093–8108.
• Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM. Pathogenesis of hepatocellular carcinoma and molecular therapies. Curr Opin Gastroenterol 2009;25: 186-194.
• 5. Kirk GD, Lesi OA, M Mendy et al. 249 (ser) P53 mutation in plasmid DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene 2005;24:5858 5867.
• Li Y, SU JJ, Qin LL, Yang C, Ban KC, Yan RQ. Synergistic effect of hepatitis B virus and aflatoxin B1 in hepato carcinogenesis in tree shrews. Ann Acad Med Singapore 1999;28: 67-71.
• Madden CR, Finegold MJ, Slagle BL. Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. J Virol 2002;76: 11770-11774.
• Weidner N. Angiogenesis as a predictor of clinical outcome in cancer patients. Hum Pathol 2000;31: 403– 405.
• Dvorak HF, Brown IF, Detmar MA, Dvorak M. Vascular permeability factor/vascular endothelial growth factor, microvascular hypermeability, and angiogenesis. Am J Pathol 1995;146:1029–1039.
• Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci 2002;7:d793– d807.
• Carr BI, Hayashi I, Branum EL, et al. Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type beta transforming growth factor. Cancer Res 1986;46: 2330– 2334.
• Nakamura T, Tomita Y, Hirai R et al. Inhibitory effect of transforming growth factor-beta on DNA synthesis of adult rat hepatocytes in primary culture. Biochem Biophys Res Commun 1985;133:1042–1050.
• Tischer E, Gospodarowicz D, Mitchell Silva RM, Schilling Lau JK, Crisp T, Fiddes JC, Abraha JA. Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family. Biochem Biophys Res Commun 1989;165:1198-1206.
• Tammela TM, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovas Res 2005;65: 550-563.
• Clifford RL, Deacon K, Knox AJ. Novel regulation of vascular endothelial growth factor-A (VEGF-A) by transforming growth factor β1: requirement for Smads, β - catenin, and GSK3 β. J Biol Chem 2008;283:35337–35353.
• Fan F, Wey JS, McCarty MF et al. Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells. Oncogene 2005;24:2647– 2653.
• Olsson A, Dimber KA, Kreuger J, et al. VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol 2006;7:359–371.
• Ferrara N, Gerber HP, LeCoute JR. The biology of VEGF and its receptors. Nature Medicine 2003;9: 669–676.
• Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci 2005;109:227–241.
• Levine A, Liu C, Greenberg XH PD, et al. Androgen induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts. Endocrinology 1998; 139:4672–4678.
• Jackson MW. A potential autocrine role for vascular endothelial growth factor in prostate cancer. Cancer Res 2002;62:854–859.
• Fukumura D, Xavier R, Suguira T, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998;94:715- 725.
• Park YN, Kim YB, Yang KM, Park C. Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis. Arch Pathol Lab Med 2000;124:1061–1065.
• Hsieh MC, Hsu HT, Hsiao PC, et al. Role of VEGF-C gene polymorphisms in susceptibility to hepatocellular carcinoma and its pathological development. J Clin Lab Anal 2014;28:237-244.
• Spinzi G, Paggi S. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:2497-2498.
• Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol 2006;12: 1175-1181.
• Leung DW, Carchianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306–1309.
• Fox SB, Gatter KC, Harris AL. Tumor angiogenesis. J Pathol 1996;179:232–237.
• Jennings MT, Pietenpol JA. The role of transforming growth factor in glioma progression. J Neurooncol 1998;36:123-140.
• Lindholm D, Castren E, Kiefer R, Zafra F, Thoenen H. Transforming growth factor-beta1 in rat brain: increase after injury and inhibition of astrocyte proliferation. J Cell Biol 1992;117: 395-400.
• Heldin CH, Miyazono K, Dijke PT. TGF-beta signaling from cell membrane to nucleus through SMAD proteins. Nature 1997;390:465-471.
• Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 2003;100:8621–8623.
• Wang J, Shao N, Ding X, Tan B, Song Wang QN, Jia Y, Ling H, Cheng Y. Crosstalk between transforming growth factor-β signaling pathway and long non-coding RNAs in cancer. Cancer Lett 2016;370:296–301.
• Pardali K, Kurisaki A, Morén A, Ten Dijke P, Kardassis D, Moustakas A. Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem 2000;275:29244–29256.
• Seoane J, Le HV, Shen L, Anderson SA, Massagué J. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 2004;117:211–223.
• Murawaki Y, Ikuta Y, Nishimura Y Koda, M, Kawasaki H. Serum markers for fibrosis and plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis, J Gastroenterol Hepatol 1996;11:443–450.
• Elliott RL, Blobe GC. Role of transforming growth factor Beta in human. J Oncol Clin 2005;23:2078-2093.
• Levy L, Hill CS. Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev 2006;17: 41-58.
• Kanzler S, Meyer E, Lohse AW, Schirmacher P, Henninger J, Galle PR, Blessing M. Hepatocellular expression of a dominant negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis. Oncogene 2001;20:5015–5024.
• Im YH, Kim HT, Kim IY, Factor VM, Hahm KB, Anzano M, Jang JJ, Flanders K, Haines DC, Thorgeirsson SS, Sizeland A, Kim SJ. Heterozygous mice for the transforming growth factor-β type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. Cancer Res 2001;61: 6665–6668.
• Ohgushi M, Kuroki S, Fukamachi H, O'Reilly LA, Kuida K, Strasser A, et al. Transforming growth factor beta- dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. Mol Cell BioL 2005;25:10017–10028.
• Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, Imai Y, Shimomukai H, Nomura Y, Matsuda Y, et al. High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 1996;110:375-382.
• Wikstrom P, Stattin P, Franck-Lissbrant I, Damber JE, Bergh A. Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate 1998;37:19-29.
• Friedman E, Gold LI, Klimstra D, Zeng ZS, Winawer S, Cohen A. High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer. Cancer Epidemiol Biomarkers Prev 1995;4:549-554.