Abstract 3138: Key role of secreted kinase FAM20C on tumor associated macrophage (TAM) leading to pancreatic cancer progression

FAM20C reported as a novel secreted kinase has the potential of phosphorylation on consensus motif, S-x-E/pS, of secretory proteins or ectodomain of membrane proteins. Numerous substrate candidates through prediction implied FAM20C has the function on tumor microenvironment, however, function and regulatory mechanism of cancer progression by FAM20C has not been defined yet. As tumor associated macrophage (TAM) changes to have the tumor supporting phenotype in response to various environmental stimuli, TAM is the potent regulatory target of FAM20C in tumor microenvironment. In this study, we hypothesized that the secreted kinase FAM20C in tumor microenvironment can support pancreatic cancer progression by regulating TAM contents or polarization. In pancreatic orthotopic xenograft model of FAM20C-overexpressing tumor cells, the tumor growth rate was enhanced and TAM contents (F4/80 + /CD11b + /MHCII + ) were significantly increased compared to control group, while total macrophage population between two groups had no difference. Moreover, the high level of TAM contents was sustained in the presence of FAM20C till the late stage of tumor progression. In addition, infiltrated tissue macrophages were polarized into TAM by FAM20C treatment Furthermore, increased TAM population by FAM20C suppresses the CD8 + cytotoxic T cell proliferation with anti-tumor function. Collectively, FAM20C might be a key regulatory factor in pancreatic cancer progression by promoting polarization of TAM. Citation Format: Jieun Im, Yu-Sun Lee, Sun Il Choi, Beom-Kyu Choi, A-Ra Jeon, Sang Hyun Park, Min-Kyeong Lee, Joon-Ki Kim, Yun-Hee Kim. Key role of secreted kinase FAM20C on tumor associated macrophage (TAM) leading to pancreatic cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3138.