Fatty acid binding protein 5 promotes tumor angiogenesis and activates the IL6/STAT3/VEGFA pathway in hepatocellular carcinoma

• Published in: Biomedicine & pharmacotherapy 2018-10, Vol.106, p.68-76
• Main Authors: Pan, Long, Xiao, Heng, Liao, Rui, Chen, Qingsong, Peng, Chong, Zhang, Yuchi, Mu, Tong, Wu, Zhongjun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Culture Media, Conditioned - metabolism; Fatty acid binding protein 5; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Female; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Interleukin-6 - metabolism; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Middle Aged; Neovascularization, Pathologic; Neovascularization, Physiologic; Paracrine Communication; Signal Transduction; STAT3 Transcription Factor - metabolism; Vascular endothelial growth factor A; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.06.040

[Display omitted] •We elucidated FABP5 as a potential agents for anti-angiogenic therapy against HCC.•FABP5 was positively correlated with VEGFA in HCC and associated with adverse HCC characteristics.•Angiogenesis of HUVECS in vitro were enhanced with increasing expression of FABP5 in HCC cells.•FABP5 activated IL6/STAT3/VEGFA pathway in HCC. Tumor angiogenesis is an essential process for facilitating tumor growth and metastasis. Fatty acid binding protein 5(FABP5)is highly expressed in hepatocellular carcinoma (HCC). Thus, we investigated the role of FABP5 in tumor angiogenesis during HCC development. In this study, the protein and mRNA levels of FABP5 in matched HCC and adjacent noncancerous liver tissues from 43 patients were determined using immunohistochemistry and real-time quantitative PCR, respectively. Two HCC cell lines (Huh7 and SMMC-7721) and human umbilical vein endothelial cells (HUVECS) were used to investigate the pro-angiogenic effect of FABP5 by tube formation, CCK8 and Transwell migration assays. The expression levels of interleukin 6 (IL6) and vascular endothelial growth factor A (VEGFA) secreted from HCC cells were detected by enzyme-linked immunosorbent assay (ELISA). In 43 HCC patients, the expression of FABP5 mRNA was positively correlated with intratumoral VEGFA mRNA expression. FABP5 mRNA expression was also associated with adverse HCC characteristics. In vitro, cell viability, cell migration and tube formation in HUVECs were enhanced with increasing expression of FABP5 in HCC cells. Downregulation of FABP5 expression inhibited the IL6/STAT3/VEGFA pathway in HCC cells and inhibited tumor angiogenesis. FABP5 was shown to promote angiogenesis and activate the IL6/STAT3/VEGFA pathway in HCC. FABP5 may be a potential antiangiogenic target in the treatment of HCC.