title: Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells.
abstract: 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.
authors: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Tao
authors: T
authors: Ren
authors: Yi
authors: Y
authors: Qing
authors: Nan
authors: N
authors: Dai
authors: Mengxia
authors: M
authors: Li
authors: Chengyuan
authors: C
authors: Qian
authors: Yuxin
authors: Y
authors: Yang
authors: Yi
authors: Y
authors: Cheng
authors: Zheng
authors: Z
authors: Li
authors: Shiheng
authors: S
authors: Zhang
authors: Zhaoyang
authors: Z
authors: Zhong
authors: Dong
authors: D
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002648:Child; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Cancer; microvessel density; osteosarcoma; tumor angiogenesis; xenograft