Abstract 474: Regulation of epithelial plasticity of cancer cells by tumor-associated macrophages

Abstract

Abstract Epithelial plasticity of cancer cells is considered to be critical for the metastatic process of cancer cells. Epithelial-mesenchymal transition (EMT) has been proved to associate with cancer metastatic dissemination from primary tumor site to distal metastatic organ. In contrast, accumulated evidence showed that the reversal process of EMT, i.e., mesenchymal-epithelial transition (MET), is critical for metastatic colonization. However, the mechanism for controlling the epithelial plasticity during metastatic process is unclear. Tumor-associated macrophages (TAMs) are the most abundant host immune cells in tumor microenvironments. TAMs have been shown to modulate cancer progression through regulating cancer cell growth and metastasis, and remodeling extracellular matrix. However, it is still unclear about the roles of TAMs in regulating epithelial plasticity during cancer metastasis. Here, we demonstrate the distinct characteristics of that the TAMs in primary and metastatic tumors. The TAMs in metastatic tumors carry a M2-like phenotype; in contrast, the TAMs in primary tumors are composed of heterogeneous population containing both M1-like and M2-like cells. Furthermore, we polarize human monocytes into M1-like and M2-like macrophages and treat cancer cells with M1 and M2 macrophages conditioned medium. We find that different macrophage subtypes have a distinct effect in modulating epithelial plasticity of cancer cells. Interestingly, polarized macrophages regulate cancer cell morphological changes through epigenetic regulation. Therefore, we propose that TAMs in tumor microenvironment may polarize into different subtypes and facilitate cancer metastatic dissemination. These findings have implications for designing alternative strategies aimed at preventing and inhibiting cancer metastasis. Citation Format: CHIH-CHAN LEE, Muh-Hwa Yang. Regulation of epithelial plasticity of cancer cells by tumor-associated macrophages. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 474. doi:10.1158/1538-7445.AM2015-474