A Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration

Luga V., et al. 2012. Cell. 2012. 151, 1542-56.

Speaker: Yu-Zhen Lu (呂瑜珍)                             Time: 14:00~15:00, Feb. 27, 2013

Commentator: Dr. Li-Jin Hsu (徐麗君 博士)      Place: Room 601

Abstract:

During tumorigenesis, a variety of stromal cells, including cancer-associated fibroblasts (CAFs), endothelial cells and inflammatory immune cells will be recruited to tumors and form tumor-associated microenvironment that can support tumor growth and invasion. Previous studies have showed that CAFs not only secret factors (HGF and SDF1) to promote cancer cells proliferation, but also interact with other stromal components to stimulate inflammation and angiogenesis. More importantly, CAFs facilitate tumor invasion and metastasis through ECM remodeling. However, the mechanisms of CAFs specifically promote cancer metastasis is less understood. The authors discovered the conditioned medium from mouse L fibroblast, called active-conditioned medium (ACM), enhanced MDA-MB-231 cells (human breast adenocarcinoma) protrusive activity and motility. Besides, they also found L cells promoted MDA-MB-231 cells invasion in mouse models. As planar cell polarity (PCP) signaling pathway controls the polarity, protrusive activity and motility of breast cancer cells, the authors showed ACM stimulated MDA-MB-231 cells to secret Wnt11 (the ligand of PCP signaling) and induce the activation of PCP signaling. To investigate the factor(s) produced by L cells to promote autocrine Wnt11-PCP signaling in MDA-MB-231 cells, the authors analyzed ACM by chromatography and proteomic analysis and revealed it was exosomes that can enhance the metastatic potential of MDA-MB-231 cells. After internalization of L-secreted exosomes, the endogenous Wnt11 in MDA-MB-231 cells would load onto exosomes and recycle back to the extracellular milieu. Taken together,   fibroblast-secreted exosomes internalized into MDA-MB-231 cells and allows the Wnt11 gain access to extracellular milieu that activates PCP signaling.

References:

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