A Novel Xenograft Model in Zebrafish for High-Resolution Investigating Dynamics of Neovascularization in Tumors

• DOI: 10.1371/journal.pone.0021768
• Publication Date: 2011-07-13T20:54:41Z
• Authors: Chengjian Zhao; Xiaofei Wang; Yuwei Zhao; Zhimian Li; Shuo Lin; Yuquan Wei; Hanshuo Yang
• Keywords: Vascular Endothelial Growth Factor A; 0303 health sciences; Indoles; Neovascularization, Pathologic; Science; Q; R; Endothelial Cells; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays; Mice; 03 medical and health sciences; Cell Line, Tumor; Neoplasms; Microvessels; Medicine; Animals; Humans; Pyrroles; Zebrafish; Research Article; Cell Proliferation

Tumor neovascularization is a highly complex process including multiple steps. Understanding this process, especially the initial stage, has been limited by difficulties of real-time visualizing embedded in tumor tissues living animal models. In present study, we have established xenograft model zebrafish implanting mammalian cells into perivitelline space 48 hours old Tg(Flk1:EGFP) transgenic embryos. With model, dynamically visualized neovascularization, with unprecedented high-resolution, new sprouts from host vessels and origination VEGFR2+ individual endothelial cells. Moreover, quantified their contributions during formation vascular network tumor. Real-time observations revealed that angiogenic tumors preferred to connect each other form loops, more loops accumulated irregular chaotic network. The over-expression VEGF165 significantly affected vascularization xenografts, not only number size neo-vessels but abnormalities architecture. specific inhibitor VEGFR2, SU5416, inhibited growth melanoma had little affects normal zebrafish. Thus, zebrafish/tumor provides unique window investigate earliest events tumoral neoangiogenesis, sensitive be used as an experimental platform rapidly visually evaluate functions angiogenic-related genes. Finally, it also offers efficient cost-effective means for rapid evaluation anti-angiogenic chemicals.