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

Lu,Yi; Lin,Nan; Chen,Zhiju; Xu,Ruiyun

doi:10.3892/mmr.2014.2689

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

Authors:
- Yi Lu
- Nan Lin
- Zhiju Chen
- Ruiyun Xu
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Affiliations: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: October 17, 2014 https://doi.org/10.3892/mmr.2014.2689
Pages: 691-697

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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.

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