Modeling Tumor Angiogenesis in Zebrafish

The process of angiogenesis is essential for tumor progression and metastasis. New pathways have been identified to play a critical role in promoting and regulating blood vessel formation both in embryogenesis and in pathophysiological conditions. These pathways provide potential molecular targets for anti-angiogenic therapies to treat cancer and other vascular diseases. The critical cellular targets of these therapies are vascular endothelial cells (ECs) and supporting mural cells or pericytes (MCs) that are recruited from surrounding healthy tissue to form new vessels in the growing tumor. A challenging task has always been to visualize these biological processes in vivo as well as to screen for drugs affecting these pathological pathways. In this context, the zebrafish model represents an emerging vertebrate system to study the tumor angiogenesis process and to better understand the modification of tumor microenvironment by anti-angiogenesis therapy. Can a small tropical fish help to better understand the tumor angiogenesis process and identify new therapies for tumor angiogenesis ? In this chapter we illustrate how the zebrafish has emerged as a novel in vivo cancer model to study tumor-induced neovascularization and metastases. In the transparent zebrafish embryos, invasion and migration of tumor cells, their circulation in the vascular system, as well as the formation tumor-induced neovascularization can all be followed with high resolution in real time. Importantly, these zebrafish models allow to quantitate both metastatic behavior of transplanted tumor cells and tumor-cell induced neovascularization. The zebrafish model has the advantage of being a vertebrate equipped with easy and powerful genetic and imaging tools to investigate the mechanisms of tumor development and progression. In particular the transparency of embryos and lately also adult are transforming this model system in the leading in vivo model for cancer biology and tumor angiogenesis.