title: VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis.
abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA3.1 empty vector, pcDNA3.1-VEGF111b or pcDNA3.1-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth.
authors.affiliation: Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gu
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016685:Mitomycin
keywords: Anti-angiogenesis; DSS; FBS; HRP; HUVECs; PSS; RT-PCR; Splice variant; VEGF; VEGF receptor; VEGF-R; VEGFR-2; VEGFxxxb; fetal bovine serum; horseradish peroxidase; human umbilical vein endothelial cells; istal splice site; proximal splice site; reverse transcriptase-PCR; vascular endothelial growth factor