Role of syndecan-4 in resistance to cell death associated with substrate adhesion impediment (anoikis) in endothelial cells in culture

• Grant number: 09/54653-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2010
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Cristina Lopes de Azevedo
• Grantee: Carla Cristina Lopes de Azevedo
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Syndecan-4 can act as co-receptor for growth factors and proteins of the extracellular matrix (ECM), increasing the affinity of these molecules to their specific receptors. Syndecan-4 participates in cell adhesion at focal contacts with integrins and FAK (focal adhesion kinase), connecting the ECM to cytoskeleton. Changes in the expression of syndecan-4 have been found in tumor cells, indicating their involvement in cancers. The acquisition of resistance to cell death induced by blockade of adhesion to the substrate (anoikis resistance) is a feature of neoplastic transformation and a critical step during the metastatic process. As syndecan-4 is involved in cell adhesion, this project aims to study: the tumorigenic capacity, the adhesion capacity, the cell cycle, the expression and location of syndecan-4, the synthesis of sulfated glycosaminoglycans (GAGs), the cell survival pathways, the ECM molecules, the phosphorylated proteins involved in pathways of cell survival after stimulation with NO donor drugs, the expression of the eNOS enzyme (endothelial NO synthase), when endothelial cells from rabbit aorta are subjected to transformation induced by blockade of adhesion. This study will provide new subsidies for understanding the process of metastasis. Resistance to anoikis is a prerequisite for tumor invasion and metastasis and may represent an important therapeutic target. (AU)