Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells.
Bottom Line: 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.
Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.Show MeSH
Related in: MedlinePlus
Mentions: A total of 80 separate osteosarcoma tissue blocks were processed using immunostaining and analyzed for APE1, FGF2, FGER3 and CD34. APE1 antibody staining was mostly localized in the nucleus and the cytoplasm. Out of the total of 80, 55 cases (68.8%) exhibited high levels of APE1 expression (Fig. 1a) and 46 cases (57.5%) consistently showed high expression of FGF2 and FGFR3 (Fig. 1b,c) in the cytoplasm of tumor cells and epithelium of new capillaries. A microvessel is defined as any endothelial cell that is CD34-positive. CD34 antibody staining was mainly localized in the cytoplasm and membrane of vascular endothelial cells in tumor stroma (Fig. 1d). The MVD value in the tumor sections varied from 7 to 93 microvessels per 200× field.
Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.