Abstract 5087: EMT in cancer cells promotes the extracellular matrix remodeling by cancer-associated fibroblasts

Abstract

Abstract Microenvironmental factors in tumor tissue induce epithelial-mesenchymal transition (EMT) in cancer cells. However, it remains unclear how EMT-induced cancer cells affect mechanisms of invasion by cancer-associated fibroblasts (CAFs). In this study, we investigated how EMT-induced cancer cells develop supportive functions of CAFs in the process of local invasion. Using an in vitro collagen invasion assay model, EMT-induced cancer cells invaded the collagen matrix to a greater extent compared to control cells when they were cultured alone. Interestingly, CAFs co-cultured with EMT-induced cancer cells invaded to a greater extent compared to those with control cancer cells. We revealed that platelet-derived growth factor (PDGF)-B was upregulated in EMT-induced cancer cells, and the invasion ability of CAFs decreased by shRNA knockdown of PDGF-B in EMT-induced cancer cells. Treatment of a PDGF receptor inhibitor cancelled the increased invasion abilities of CAFs and EMT-induced cancer cells. Our results indicated that EMT-induced cancer cells enhanced the CAF invasion ability through the secretion of PDGF-BB as well as increased the invasion ability themselves, suggesting that EMT-induced cancer cells in the tumor microenvironment could not only exhibit their increased invasion but also promote CAF invasion which might lead to local invasion of cancer cells. Citation Format: Shinya Neri, Genichiro Ishii, Atsushi Ochiai, Toshi Menju, Makoto Sonobe, Hiroshi Date. EMT in cancer cells promotes the extracellular matrix remodeling by cancer-associated fibroblasts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5087.