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Tumor migration and invasion mediated by RECK gene in human metastic melanoma cell lines

Grant number: 11/18142-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2011
Effective date (End): October 31, 2012
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Silvya Stuchi Maria-Engler
Grantee:Taissa de Mattos Faria
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanoma is the most aggressive form of skin cancer and represents a major cause of death from this disease, mainly in young adults. The resistance of this tumor to most antitumor drugs has been a huge challenge to the scientific community, which made necessary to develop new therapeutic strategies. Resistance to death by apoptosis in response to chemotherapy and other external stimuli provide a selective advantage for tumor progression, metastasis formation and therapy resistance. Melanoma accumulates a series of changes in gene expression that contribute to uncontrolled proliferation, evasion of senescence and inhibition of cell death in multiple intracellular routes. The RECK gene, the subject of this study, has important features throughout tumor progression. It is a cytoplasmic membrane-anchored protein able to negatively regulate metalloproteinases (MMPs). MMPs degrade the extracellular matrix, contributing to the formation of a microenvironment favorable to tumor growth and metastasis. The RECK gene is present in different normal human tissues. However, by analyzing its expression in various tumor cell lines, has been shown to be low or not detected. When RECK is overexpressed in different malignant cell lines, the secretion of MMPs is reduced and the invasive and metastatic capacity is suppressed, indicating an inverse correlation between RECK expression and tumor invasion and metastasis. Thus, this study aims to evaluate the effects of RECK in human metastatic melanoma cell lines in order to assess the parameters involved in cell migration and invasion.