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
| Autor: | Yi Lu, Nan Lin, Zhiju Chen, Ruiyun Xu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Hepatic stellate cell proliferation
Vascular Endothelial Growth Factor A Cancer Research Carcinoma Hepatocellular Angiogenesis Becaplermin Gene Expression Biology Biochemistry Receptor Platelet-Derived Growth Factor beta Paracrine signalling Cell Movement Cell Line Tumor Genetics Hepatic Stellate Cells Humans Hypoxia Molecular Biology Cell Proliferation Cell growth Liver Neoplasms Proto-Oncogene Proteins c-sis digestive system diseases Coculture Techniques Vascular endothelial growth factor A Oncology Cancer research Hepatic stellate cell Molecular Medicine Ectopic expression A431 cells |
| Zdroj: | Molecular medicine reports. 11(1) |
| ISSN: | 1791-3004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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