Estudo da infecção por Trypanosoma cruzi em células normais e tumorais de mama

Abstract

Among women, breast cancer is the most common neoplasm and has the highest mortality rate. Triple-negative breast cancer (TNBC) is a tumor subtype characterized by the absence of receptors and consequent lack of treatments.. Most deaths caused by breast cancer are not due to the primary site of the tumor, but to the formation of metastases in other organs. Therefore, chemokines and receptors play a crucial role in this clinical picture, as they regulate the migration of tumor cells. Thus, several target molecules are studied, among them is the chemokine receptor CXCR4 and its ligand CXCL12. In this context, the P21 protein secreted by Trypanosoma cruzi plays a fundamental role in the regulation of the CXCR4/CXCL12 axis. Recently, rP21 is known to bind to the CXCR4 receptor on MCF-10A cells (non-tumor cells) and MDA-MB-231 (triple-negative breast cancer cells), interfering with migration/invasion phenotypes and proliferation of these cells. Thus, this study aimed to evaluate the cellular invasion and multiplication of T. cruzi in normal and human breast tumor cells and the cell migration of both cell lines infected by T. cruzi. Our data showed that MDA-MB-231 cells have a higher rate of invasion by T. cruzi and that the parasite replicates more in MCF-10A cells. Thus, both cells were found to be susceptible to infection by T. cruzi, and MDA-MB-231, due to its greater release of amastigote forms in the supernatant, and less formation of nests, was more susceptible to infection. Furthermore, we demonstrated that T. cruzi significantly reduces cell migration of both cell lines from ligand to the CXCR4 receptor. Therefore, like rP21, T. cruzi has antitumor characteristics acting as an antagonist of the main ligand of the CXCR4 receptor.