title: Connexin 43 suppresses tumor angiogenesis by down-regulation of vascular endothelial growth factor via hypoxic-induced factor-1α.
abstract: Previous work showed that connexin 43 (Cx43) reduced the expression of hypoxic-induced factor-1α (HIF-1α) in astrocytes. HIF-1α is a master transcription factor for angiogenesis in tumor. Angiogenesis is essential for tumor progression. Here, we investigated the role of Cx43 in vascular endothelial growth factor (VEGF) production and angiogenesis in murine tumor. In the study, mouse B16F10 and 4T1 cells were overexpressed or knockdown with Cx43. The expression profiles as well as activity of the treated cells were examined. Furthermore, reduced Cx43 expression in B16F10 and 4T1 cells causes increased expression of VEGF and enhanced the proliferation of endothelial cells. On the contrary, the expression of VEGF and the proliferation of endothelial were increased in the conditioned medium of Cx43-knockdown tumor cells. We subcutaneously transplanted Cx43-overexpressing B16F10 cells into mice to evaluate the roles of Cx43 in the tumor angiogenesis. Both tumor size and the number of vessels growing in the tumor were markedly decreased compare with control group. Our findings suggest that Cx43 inhibited tumor growth by reducing angiogenesis.
authors.affiliation: Department of Environmental Engineering and Science, Feng Chia University, Taichung 40407, Taiwan. wkwang@fcu.edu.tw.
authors.forename: Wei-Kuang
authors.initials: WK
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40404, Taiwan. menny628@hotmail.com.
authors.forename: Man-Chin
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung 40404, Taiwan. isaac_leong725@hotmail.com.
authors.forename: Hon-Fai
authors.initials: HF
authors.lastname: Leong
authors.affiliation: School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40402, Taiwan. yuliangkuo@mercury.csmu.edu.tw.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40404, Taiwan. u100004422@cmu.edu.tw.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40404, Taiwan. chlee@mail.cmu.edu.tw.
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A