Proteases and Extracellular Matrix
Dr. Juan Carlos Rodríguez Manzaneque
Scientific interest areas
The understanding of tumor angiogenesis, basic component for the growth of solid tumors and for the development of metastasis, has suffered great advances during the last years. During the complex formation of tumor neo-vasculture there are many relevant factors, including the major role that extracellular proteases exert at the tumor microenvironment.
The unique contribution of the genomic era revealed the enormous complexity of the extracellular framework, far from the simplistic view of a scaffold and maintenance service. Together with the functional characterization of every existing extracellular protease, it is required to envision such proteolytic activity in a specific scenario. The identification of the specific substrates (“Degradomics”) is a major goal of the scientific community, although it is needed the translation of these findings to proper biological models.
The dynamism of the extracelular milieu is closely related to the functional properties of neo-vascularization events, important for its development, for the appearance of metastasis, and also for the success or fail of therapies. Also, it has been described a major role of the extracellular matrix for the determination of a specific cellular phenotype from a stem cell. Again, it is obvious the inspiring parallelism among the biology of development and the biology of tumors, highlighted by the new challenge that the characterization of cancer stem cells brings up. These cellular entities appear as a paradigm of cellular plasticity, and recent findings show the mimetic capacity of tumor cells to acquire specialized phenotypic properties, including the participation in processes of neo-vascularization.
The detailed characterization of the tumor microenvironment and its remodelling by proteolysis, together with the extracellular and cellular components of the vascular niche, are a current priority, with special relevance for the understanding of mechanisms of drug resistance that certain tumors develop. The convergence of advanced platforms of genomic analysis, together with the functional study of extracellular components in the aberrant scenario of a tumor, appeared as a reliable scenario to investigate for the best knowledge of tumor progression.