Study of proliferation and cell death in melanocytes and melanoma by ATP and analogues through the activation of receptors P2.

• Grant number: 09/02818-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2010
• End date: February 29, 2012
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Alice Teixeira Ferreira
• Grantee: Jorge Wilson Carriço
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The melanoma is a very aggressive cancer with high mortality in metastatic stage. One of the main characteristics of cancers, as well as melanoma, is the uncontrolled proliferation and the reduction of the process of cellular death. According to estimates the National Cancer Institute (INCA), in Brazil in 2008, the melanoma affects around 6,000 people and is in tenth position in the incidence of cancer in the country. However, the incidence of this cancer mortality is one of the first placed, because of its high aggressiveness in metastatic stage. The ATP (adenosine 5'-triphosphate) is an important signaling molecule, acting on P2 receptors. Recent studies showed that extracellular ATP promotes the activation of P2X and P2Y receptors, stimulating the release of intracellular calcium (Ca2+i), which operates in different mechanisms related to proliferation and cell death. Different subtypes of P2 receptors have been identified in a variety of cancers and current work suggests that some P2 receptors may mediate different pathophysiological roles in several types of tumors, such as proliferation and cell death. Our previous results showed that low concentrations of ATP cause increased cell proliferation in melanocytes and melanoma cells, and that high concentrations of agonist causing cell death mainly in cancer cells, not damaging the healthy cells (in vitro study), making It is therefore important to target the development of future therapies. We believe that a better understanding of the signaling pathways involved in proliferation and cell death mainly in cells of healthy and cancer considering different concentrations of ATP and analogues, and better understanding of the involvement of Ca2+i, in both cases, it may assist in the development of protocols that provide the selective death of cancer cells without major damage to healthy cells. Thus, the objective of this project is to analyze and compare the proliferation and cell death of melanoma (Tm5) and melanocyte murine cells (melan-a) induced by ATP and analogues in different concentrations, verifying the possible signaling cascades involved in these processes and relate the types of P2 receptors involved.