The alfa2beta1 integrin in breast tumor progression: the role in tumor microenviro...
| 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 |
Abstract
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)