Abstract 4605: Exosomes harvested from patient-derived-explants or cells-enhance proliferation and migration in TNBC breast cancer cells and breast epithelial cells

Abstract

Abstract Triple negative breast cancer (TNBC) is a clinically aggressive breast cancer subtype due in part by high rates of metastasis and poor prognoses. TNBC tumors are molecularly heterogeneous and lack targetable receptors common in other breast cancer subtypes (estrogen receptor, HER2/Neu amplification), hindering the discovery of effective targeted therapies. Our group has designed a series of experiments to gain insight into the role of the tumor microenvironment in TNBC proliferation, migration and invasion. Patient-derived xenografts (PDXs) are translational models that are necessary to use in the laboratory setting when studying the complex tumor microenvironment of TNBC tumors. Recent breast cancer-focused studies show exosomes can be local and systemic cell-to-cell transporters of oncogenic information. Here, we aim to better understand how tumor-derived exosomes harvested from TNBC PDX models affect cell proliferation and migration when cultured with either triple negative breast cancer cell line MDA-MB-231 or non-tumorigenic breast epithelial cell line MCF-10A. PDX tumors or cells were plated in 2D culture conditions, and exosomes were isolated and purified from the cell culture media. Proliferation and migration assays were then performed after co-culture of the exosomes (or RPMI-1640 media as a negative control) with breast cell lines (MDA-MB-231, MCF-10A). The Alamar blue dye exclusion assay was used to measure proliferation, and absorbance was measured to quantify relative proliferation amongst the different treatment groups. To evaluate cell migration, a transwell migration assay was utilized where the breast cancer cell lines were plated with either the exosomal media or standard growth media as the chemoattractant for 48 hours. For invasion experiments, the transwell migration assay was employed. Our data indicate that TNBC PDX-derived exosomes increased cell proliferation in the MDA-MB-231 cell line by an average of approximately 60% compared to the control (p ≤ 0.05). We observed similar patterns of increased cell proliferation in the MCF-10A cell line, with an increase of 34% when cells were exposed to exosomes (p ≤ 0.05) compared to the control. Exosomes from TNBC PDX models increased migration in MDA-MB-231 cells by 4% and in MCF-10A cells by 10 percent. Interestingly, when we screened the exosomes from different TNBC PDX models, we found that one invasive TNBC PDX model contributed to the increased proliferation and migration in both the MDA-MB-231 and MCF-10A cell lines. Exosomes harvested and purified from TNBC patient-derived explants, and 2D culture conditions models increased proliferation and migration, cell line MDA-MB-231, and the non-tumorigenic breast epithelial cell line MCF-10A. Our data suggests that exosomes are key mediators in the progression of cancer. Note: This abstract was not presented at the meeting. Citation Format: Jordon Coward, Margarite D. Matossian, Paige A. Roberts, Jasmine Johnson, Matthew E. Burow, KiTani P. Lemieux. Exosomes harvested from patient-derived-explants or cells-enhance proliferation and migration in TNBC breast cancer cells and breast epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4605.