Evaluation of circulating microparticles derived from invasive ductal breast adenocarcinomas Her2+ patients and it's possible correlation with tumor aggressiveness

Abstract

¬Microparticles (MPs) derived from the plasmatic or endosomal membranes have important roles in the inter-cellular communication. MPs arise from many cell types, such as endothelial cells, leukocytes, stem-cells and tumor cells and are produced during many cell processes such as, cell differentiation, stress, senescence and others. MPs roles are related to the biological contexts that determine their content and the cellular pathways that trigger their synthesis. They can carry mRNAs, microRNAs and proteins that can be delivered to nearby cells, or even to distant tissues. In cancer, it has been shown that this delivery has an important role on tumor progression and metastasis development. In order to evaluate a putative correlation between MPs present in the plasma from patients with breast invasive ductal carcinoma (IDC) Her2+ and tumor aggressiveness, we will evaluate MPs isolated from 3 patient groups with progressive stages of cancer disease: a) tumors with no positive lymph nodes or distant metastasis, b) tumors with positive lymph nodes and no distant metastasis and c) tumors with positive lymph nodes and metastasis. The identification and the determination of expression levels of mRNA species, miRNAs and proteins present in the MPs will be analyzed from each group sample, as well as among the different groups, and this may reveal relevant markers for early tumor detection and determination of disease prognosis. The involvement of MPs in tumor progression and aggressiveness will be evaluated by in vitro proliferation, migration and invasion assays using two human breast tumor cell lines overexpressing Her2 and a human breast tumor cell line that doesn't express Her2. Also, the supposed relation of MPs with angiogenesis will be investigated by in vitro capillary-like tube-formation assays on human umbilical vein endothelial cells. There are no publications relating the study of plasma MPs in patients with IDC Her2+, and we trust this project should contribute to a better understanding of the biology of these tumors. (AU)