Abstract
We report here real-time color-coded imaging of osteosarcoma-induced angiogenesis in vivo. Gelfoam® (5×5 mm) treated with β fibroblast growth factor (bFGF) was initially transplanted subcutaneously in the flank of transgenic nestin-driven green fluorescent protein (ND-GFP) nude mice (n=12). In ND-GFP mice, nascent blood vessels are labeled with GFP, including those growing in Gelfoam®. Seven days after transplantation of Gelfoam®, skin flaps were made and human 143B osteosarcoma cells expressing GFP in the nucleus and red fluorescent protein (RFP) in the cytoplasm were injected into the transplanted Gelfoam®. The control group had only Gelfoam® transplanted without subsequent cancer-cell inoculation. Skin flaps were made at days 14, 21, 28 after transplantation of the Gelfoam® to allow observation of vascularization of the Gelfoam® using fluorescence imaging after both with and without cell inoculation. ND-GFP expressing nascent blood vessels penetrated and spread into the Gelfoam® in both the non-cellular control and after cancer-cell inoculation. The mean length of ND-GFP expressing blood vessels of mice with osteosarcoma cells seeded on the Gelfoam® increased compared to the Gelfoam®-only control at days 14, 21, 28 after transplantation of the Gelfoam® (at day 14, 21 ; p<0.05, at day 28 ; p<0.01). The results demonstrate that the osteosarcoma cells stimulated angiogenesis within the Gelfoam®. This model enables facile imaging of cancer-cell-induced angiogenesis and the study of its mechanism and inhibition.
Citation Format: Fuminari Uehara, Yasunori Tome, Hiroki Maehara, Fuminori Kanaya, Shinji Miwa, Yukihiko Hiroshima, Shuya Yano, Mako Yamamoto, Yasunori Matsumoto, Robert M. Hoffman. Real-time in vivo imaging of osteosarcoma angiogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5. doi:10.1158/1538-7445.AM2014-5
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