Vascular endothelial growth factor (VEGF) was considered as a critical growth factor for tumor expansion. The roles of VEGF121, VEGF165, and VEGF189 in tumor growth have been intensely investigated; however, involvements of another extracellular matrix (ECM)-binding VEGF isoform, namely VEGF183 (six amino acids shorter than VEGF189 in exon 6a), in physiological or pathological processes are still unclear although the wide tissue distribution. To investigate the role of VEGF183 in carcinogenesis, we generated murine breast cancer cell (EMT-6) clones stably overexpressing VEGF183, VEGF121, VEGF165, and VEGF189 shortened as V183, V121, V165, and V189, respectively. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) results showed that VEGF183, like all other VEGF-overexpressing isoforms except for VEGF121, could enhance the proliferation of mouse breast cancer EMT-6 cells. Immunochemistry results displayed that overexpressing VEGF183 and VEGF189 in EMT-6 cells induced larger proportional dilated microvessels. On the other hand, results from cell wound healing experiments demonstrated that all of the VEGF-overexpressing isoforms could increase the chemotaxis of EMT-6 cells in vitro. In conclusion, our results supported the idea that overexpression of VEGF183 promotes murine breast cancer cell proliferation in vitro and induces dilated intratumoral microvessels, and it plays a dissimilar role in comparison with that of VEGF189.
Vascular endothelial growth factor Breast cancer Angiogenesis Overexpression
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This work was supported in part by Basic Science and Frontier Technology Planning Project of Henan Province (Grant No. 142300410027), Educational Commission of Henan Province (Grant No. 12B320021), and Scientific Research Fund of Xinxiang Medical University (Grant No. 2013ZD110). We also thank Dr. Didier Meko’o for helping us polish the manuscript.
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