title: Hypoxia-induced secretion of platelet-derived growth factor-BB by hepatocellular carcinoma cells increases activated hepatic stellate cell proliferation, migration and expression of vascular endothelial growth factor-A.
abstract: Angiogenesis has an important function in the proliferation and metastasis of hepatocellular carcinoma (HCC) under a hypoxic tumor microenvironment. Activated hepatic stellate cells (HSCs) infiltrate the stroma of liver tumors and potently increase angiogenesis through tumor-stromal interactions, however, the exact mechanism by which this occurs is unknown. The present study aimed to investigate the paracrine effects of HCC-derived platelet-derived growth factor-BB (PDGF-BB) on HSCs under hypoxic conditions. It was demonstrated that PDGF-BB expression was markedly increased in HepG2 cells exposed to hypoxia. Conditioned medium (CM) from HepG2 cells stimulated LX-2 cell proliferation, migration and vascular endothelial growth factor-A (VEGF-A) expression. It was then determined that blocking PDGF-BB expression in HepG2-CM abolished these effects on LX-2 cells. The ectopic expression of PDGF-BB in HepG2 cells strongly affected LX-2 cell proliferation, migration and VEGF-A expression. In conclusion, the present study suggests that hypoxia-induced PDGF-BB secretion by HCC cells stimulates HSCs to accumulate and proliferate in the tumor stroma and the enhanced VEGF-A expression in HSCs may promote HCC angiogenesis.
authors.affiliation: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Zhiju
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Xu
mesh_terms: D000077214:Becaplermin; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta