Open AccessApurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells
Author(s) -
Ren Tao,
Qing Yi,
Dai Nan,
Li Mengxia,
Qian Chengyuan,
Yang Yuxin,
Cheng Yi,
Li Zheng,
Zhang Shiheng,
Zhong Zhaoyang,
Wang Dong
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12334
Subject(s) - angiogenesis , cancer research , small interfering rna , fibroblast growth factor , biology , neovascularization , downregulation and upregulation , basic fibroblast growth factor , growth factor , receptor , transfection , cell culture , biochemistry , gene , genetics
Tumor angiogenesis contributes to inferior prognosis in osteosarcoma. Apurinic/apyrimidinic endonuclease 1 (APE1) and fibroblast growth factor 2 (FGF2) and its receptor 3 (FGFR3) signaling pathway plays an important role in the angiogenic process. In this study we observed that high expression of APE1, FGF2 and FGFR3, and microvessel density are positively correlated with poor prognosis of osteosarcoma patients. Furthermore, the Cox model showed that the tumor size, FGF2 and its receptor 3 (FGFR3), and microvessel density were adverse prognostic factors. Based on our clinical data, and the fact that APE1 is involved in tumor angiogenesis, we hypothesize that it is very likely that APE1 may indirectly promote angiogenesis by upregulating fibroblast FGF2 and FGFR3. Our preliminary data show small interfering RNA‐mediated silence of APE1 experiments, which further supports this hypothesis. APE1‐small interfering RNA significantly inhibited tumor angiogenesis by downregulating in vitro expression of FGF2 and FGFR3 in human umbilical vein endothelial cells in Matrigel tube formation assay, and further inhibited tumor growth in vivo in a mouse xenograft model. Thus, the proposed APE1‐FGF2 and FGFR3 pathway may provide a novel mechanism for regulation of FGF2 and FGFR3 by APE1 in tumor angiogenesis.