Abstract B62: Proteomic dynamics of stromal exosomes during processing in cancer cells

Abstract

Abstract Within the tumor microenvironment, cancer-associated fibroblasts (CAFs) are capable of releasing exosomes, small extracellular vesicles, which are then used by breast cancer cells to aid in metastasis. Exosomes are uptaken by the cancer cells and gain Wnt11 through processing, thus allowing them to stimulate Wnt-signaling pathways that causes increased cell motility. Our current research has focused on understanding the events that exosomes undergo as they pass through breast cancer cells. Exosomes from L cells carry the tetraspanin, Cd81, and two of its known transmembrane interactors Igsf8 and Ptgfrn. By using immunoprecipitation, we were able to isolate Cd81-exosomes, and analyze them by mass spectrometry. Furthermore, comparison of Cd81-exosomes before and after processing in MDA-MB-231, a human breast cancer cell line, revealed differences in protein content of the exosomes. Additionally, since L cells are a mouse fibroblast cell line, we could identify the origin of each protein based on variance between human and mouse proteins. Several families of proteins were identified, such as RNA-binding proteins, kinases, phosphatases, and secretory and endocytic proteins. Our data allows us to postulate that Cd81-exosome processing involves the use of the cancer cell endocytic and secretory pathways. By determining the mechanism whereby breast cancer cells use Cd81-exosomes as signals, it may be possible to block this process and prevent or slow metastatic events. Citation Format: Ainsley Q. Underhill, Yingyi Amy Zhang, Liang Zhang, Valbona Luga, Jeff Wrana. Proteomic dynamics of stromal exosomes during processing in cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B62.