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Galectin-3 expression modulation regarding pH and oxygenation selective pressures: a mechanism for tumor heterogeneity?

Grant number: 12/19665-0
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2013
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Roger Chammas
Grantee:Ana Carolina Ferreira Cardoso
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The heterogeneity observed in human tumors is an extremely important phenomenon for understanding tumor progression and response to therapeutic intervention. Several factors, such as altered pH levels and oxygenation, contribute to the tumor heterogeneity by inducing genetic alterations or modifications in the tumor cell gene expression. With the performance of these different selective pressures, it is suggested the coexistence of multiple tumor cell populations, which assume different survival strategies. Galectin-3 (gal-3) is a b-galactoside binding protein which is involved in the tumor microenvironment adaptation, such as hypoxia, deprivation of nutrients and drug pressures. In our laboratory, we found a de novo expression of gal-3 in tumors arising in knock-out (KO) animals inoculated with murine melanoma cells that have the galectin-3 promoter silenced by methylation. This work tries to understand which factors influence the tumor gal-3 expression and what is the consequence of this for tumor progression. Therefore, it is our intention to determine whether the gal-3 expression is altered in vitro by changes in oxygenation and acidity, as well as evaluate in vivo whether a gal-3 heterogeneous tumor has a greater chance to establish and grow compared to a non heterogeneous tumor.