Breast cancer is an important public health problem. The microenvironment in which cancer cells are found plays an important role in tumorigenesis and tumor progression. Our laboratory studies the role of laminin and its bioactive peptides in tumor biology. We found that the C16 peptide derived from laminin-111 regulates the differential gene expression in breast tumors (DE SOUZA SANTOS, 2011). The C16 peptide, present on the short arm of the gamma chain 1 stimulates gene expression of SPOCK1 and GPNMB. These results were obtained in breast tumor line MDA-MB-231. In this project, we will evaluate the action of the C16 peptide in the expression of molecules encoded by genes GPNMB and SPOCK1 that, beyond of to regulating cell adhesion, migration and metastasis, may be potential tumor biomarkers. Thereby, we use lines of breast cancer with different behaviors, such as MBA-MB-231 (basal-like, triple-negative for estrogen, progesterone and HER2) and MCF-7 (luminal B HER2 positive). For comparative purposes we will use the normal cells of the breast (MCF-10A). The three lines will be handled by C16, the expression of GPNMB and SPOCK1 analyzed by immunoblot. To correlate protein expression and cellular function, we will investigate whether the C16 peptide induce invasiveness of tumor cell lines MDA-MB-231 and MCF-7. Additionally, by blocking the function for antibodies, and analyze whether GPNMB and SPOCK1 were related to invasion perhaps triggered by the peptide. Finally, in order to contextualize our results in vivo in vitro study the potential role of GPNMB and SPOCK1 as tumor biomarkers, through immunodetection of these molecules in normal and tumor breast tissue, using blades Tissue Microarrays (TMAs). We will seek to correlate the expression profile of these molecules with patients' clinical data, including staging and survival curve.
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