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Integrin molecular mechanisms of action during tumor progression and metastasis development: an intercellular approach

Grant number: 19/11437-7
Support type:Regular Research Grants
Duration: August 01, 2019 - July 31, 2021
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Heloisa Sobreiro Selistre de Araújo
Grantee:Heloisa Sobreiro Selistre de Araújo
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil


Integrins are heterodimeric cell surface receptors that connect cells to the extracellular matrix (ECM) and control various processes such as cell migration, cytoskeletal organization, cell polarity, metalloprotease activity, collagen synthesis, and migration direction. The pattern of integrin expression may be greatly altered in cells that underwent tumor transformation when compared to normal cells. Integrin-mediated signaling also modulates the response triggered by the activation of growth factor receptors such as VEGF/VEGFR, resulting in pro- or anti-angiogenic signals depending on the pathway involved. Therefore, integrins have been studied as possible targets of pharmacological inhibition for the treatment of cancer and for the prevention of metastases. However, despite excellent results in preclinical trials, integrin inhibitors have not been successful in clinical trials, probably because of our limited knowledge of the molecular mechanisms of action of these receptors. In this project, we intend to contribute to the increase of knowledge of the role of avb3 and a2b1 integrins in the metastatic cascade. We will use in vitro models of co-culture to mimic the extravasation of tumor cells from the circulation and two well characterized disintegrins as specific ligands of these receptors. In addition, we will use a quasi-vivo system which will add complexity to the assay, similar to most in vivo assays. Functional, morphological and biochemical analysis will be performed, aiming also a search for new pharmaceutical targets for metastasis prevention or treatment. (AU)