Organtropic Metastatic Secretomes and Exosomes in Breast Cancer.

摘要

Metastasis to distant vital organs (bone, lung, brain) is the most devastating feature of breast cancer. We proposed to extend our current integrative genomic, proteomic and transcriptomic analysis on the crosstalk between breast cancer cells and bone and lung microenvironments during organ-tropic metastasis. An understanding of secreted metastasis regulators (extracellular proteins, cell-free nucleic acids and small vesicles -exosomes-) has tremendous potential to improve the diagnosis, prognosis and treatment of breast cancer. We hypothesized that tumor and stromal cells communicate via secreted and exosomal proteins and miRNAs to promote organotropic metastasis. Therapeutic disruptions of these communication pathways may significantly increase diagnostic options, improve treatment efficacy and survival of breast cancer patients. The objectives of our proposal are to comprehensively analyze secreted and exosomal proteins and miRNAs that are regulators of bone and lung metastasis, to characterize their function in mediating tumor-stroma interactions, and to determine the potential of utilizing such circulating factors as biomarkers and therapeutic targets. Our specific aims are: 1) Identification and functional characterization of secreted factors promoting bone and lung metastasis; 2) Determination of the role of exosomes in metastatic progression and niche formation; 3) Clinical analysis of metastatic secretome and exosomes.