Protease ADAMTS1 influencing breast cancer behavior and microenvironment

Abstract

We have been studying the role of different proteases in tumor biology (Franca et al. 2001; Freitas & Jaeger 2002; Freitas et al. 2004; Pinheiro et al. 2004; Freitas et al. 2007; Morais Freitas et al. 2007; Freitas et al. 2008; Gama-de-Souza et al. 2008; Jaeger et al. 2008; Nascimento et al. 2010). Previous results showed that ADAMTS-1 regulates migration of breast cancer cells in culture. This project will extend our previous results on the role played by ADAMTS-1 in breast cancer biology. The in vivo expression of this protease will be assessed in different breast tumors. Clinical-pathological data and survival curves will be obtained, in order to compare tumors with ADAMTS-1 expressed or not. We will also establish an in vitro model to study regulatory mechanisms underlying ADAMTS-1 effects in tumor cells. Mammary cell lines (MCF10A, MCF-7, and MDA-MB-231) will be treated by hormones and growth factors related to breast cancer, such as estrogen, progesterone and androgen. After treatment, ADAMTS-1 levels (protein and mRNA) will be evaluated. We will also investigate whether ADAMTS-1 would influence receptors for estrogen, progesterone and androgens. Finally, the role played by ADAMTS-1 regulating tumor microenvironment will be addressed. This analysis will include following experimental conditions: 1) co-culture; 2) presence of ADAMTS-1 in matrices extracted from mammary cancer; 3) tumor cells with ADAMTS-1 silenced by siRNA and subjected to nude mice xenografts. (AU)