Open AccessApurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β‐dependent manner in human osteosarcoma
Author(s) -
Jiang Xuan,
Shan Jinlu,
Dai Nan,
Zhong Zhaoyang,
Qing Yi,
Yang Yuxing,
Zhang Shiheng,
Li Chongyi,
Sui Jiangdong,
Ren Tao,
Li Mengxia,
Wang Dong
Publication year - 2015
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.12763
Subject(s) - angiogenesis , osteosarcoma , cancer research , transforming growth factor , gene silencing , biology , metastasis , dna (apurinic or apyrimidinic site) lyase , ap site , cancer , microbiology and biotechnology , dna repair , dna , biochemistry , genetics , gene
Angiogenesis plays an important role in tumor growth and metastasis and has been reported to be inversely correlated with overall survival of osteosarcoma patients. It has been shown that apurinic/apyrimidinic endonuclease 1 ( APE 1), a dually functional protein possessing both base excision repair and redox activities, is involved in tumor angiogenesis, although these mechanisms are not fully understood. Our previous study showed that the expression of transforming growth factor β ( TGF β) was significantly reduced in APE 1‐deficient osteosarcoma cells. Transforming growth factor β promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. In the current study, we initially revealed that APE 1, TGF β, and microvessel density ( MVD ) have pairwise correlation in osteosarcoma tissue samples, whereas TGF β, tumor size, and MVD were inversely related to the prognosis of the cohort. We found that knocking down APE 1 in osteosarcoma cells resulted in TGF β downregulation. In addition, APE 1‐si RNA led to suppression of angiogenesis in vitro based on HUVEC s in Transwell and Matrigel tube formation assays. Reduced secretory protein level of TGF β of culture medium also resulted in decreased phosphorylation of Smad3 of HUVEC s. In a mouse xenograft model, si RNA ‐mediated silencing of APE 1 downregulated TGF β expression, tumor size, and MVD . Collectively, the current evidence indicates that APE 1 regulates angiogenesis in osteosarcoma by controlling the TGF β pathway, suggesting a novel target for anti‐angiogenesis therapy in human osteosarcoma.