Proteases and Cancer

Francisco Javier Rodríguez-Baena, Silvia Redondo-García, María del Carmen Plaza-Calonge, Rubén Fernández-Rodríguez, Juan Carlos Rodríguez-Manzaneque

The relevance of tumor vasculature has been extensively recognized, and it is still the focus of numerous lines of research for basic, translational, and clinical scientists. Indeed, the knowledge of some of its regulatory mechanisms has provoked the generation of ongoing cancer therapies. Within the context of the tumor microenvironment, the information that the analysis of the vasculature provides is very valuable, and it might reveal not just its quality and the response against a specific therapy but also its close relationship with neighboring stromal and tumor players.Studies during last decades already supported the contribution of extracellular proteases in neovascularization events, including ADAMTS. However, deeper analyses are still required to better understand the modulation of their proteolytic activity in the tumor microenvironment. Future studies will clearly benefit from existing and ongoing genetically modified mouse models.Here we emphasize the use of syngeneic models to study the vasculature during tumor progression, supported by their intact immunocompetent capacities and also by the range of possibilities to play with engineered mice and with modified tumor cells. Although various high-tech and sophisticated approaches have already been reported to evaluate tumor neovascularization, here we describe a simple and easily reproduced methodology based in the immunofluorescence detection of vascular-specific molecules. A final in silico analysis guarantees an unbiased quantification of tumor vasculature under different conditions.