Abstract
Abstract The cancer microenvironment surrounds tumors and primarily consists of fibroblasts and immune cells that cancer cells utiliaze to support their growth and invasion. Cancer-associated fibroblasts (CAFs) are the most prominent cell type in the microenvironment. They are attracted to tumors and activated by signals from cancer cells, including transforming growth factor-â (TGF-â). Following activation, CAFs display FAP on their surface, which breaks bonds in the extracellular matrix (ECM), creating space for cancer cells to migrate. CAFs also secrete cytokines, including stromal cell-derived factor-1 (SDF-1) and interleukin-6 (IL-6), to initiate this migration. This study seeks to determine if there is a link between the expression of fibroblast activation protein (FAP) and the specific production of SDF-1 and IL-6. Flow cytometry was used to verify the expression of FAP by the Malme-3 fibroblast cell line at an average rate of 50.6% and in the Malme-3M melanoma cell line at 4.8%. TGF-â treatment increased FAP expression in Malme-3M melanoma cells (50% increase), indicating a prominent role in cell transformation. siRNA transfection was also used to reduce FAP expression in both the fibroblasts (48.4% decrease) and the melanoma cells after initial TGF-â activation (11.6% decrease). Preliminary data from intracellular staining and ELISA analysis suggest that SDF-1 and IL-6 production both increased in melanoma cells in direct correlation to FAP expression in, but may be inversely related in fibroblasts. Future studies will further analyze the FAP expression levels and cytokine secretion of both cell types in different microenvironments to elucidate the relationship between FAP expression in cancer and the secretion of SDF-1 and IL-6. Citation Format: Zachary B. Fisher, Yuko J. Miyamoto. The manipulation of FAP expression and its role in SDF-1 and IL-6 secretion by fibroblasts and melanoma cells. [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 765.
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