Abstract 4341: Mesenchymal stem cells promote epithelial-mesenchymal transition of colon cancer cells via direct cell-to-cell contact

Abstract

Abstract We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to tumor stroma and promoted tumor growth and metastasis. We evaluated the proliferation and migration ability in directly and indirectly co-culture assay to clarify the mechanism of interaction between cancer cells and MSCs. Proliferation and migration ability of cancer cells were increased by direct co-culture with MSCs but not by indirect co-culture of MSCs. Thus, we thought that direct contact between cancer cells and MSCs is important to their interaction. We performed microarray analysis of gene expression in KM12SM colon cancer cells directly co-cultured with MSCs. Expression of epithelial-mesenchymal transition (EMT) related genes such as fibronectin (FN), SPARC and Galectin 1 was increased by direct co-culture with MSCs. We also confirmed the upregulation of these genes with real time PCR, and these genes were not increased in cancer cells indirectly co-cultured with MSCs. Among these EMT related genes upregulated by direct co-culture with MSCs, we examined immune localization of FN, well-known EMT marker. In co-culture assay in chamber slides, expression of FN in cancer cluster was seen only at the edge where cancer cells directly contacted with MSCs. FN expression by cancer cells was increased at the tumor periphery and invasive edge in orthotopic nude mice tumors and human colon cancer tissues, respectively. These results suggest that mesenchymal stem cells induce epithelial-mesenchymal transition of colon cancer cells via direct cell-to-cell contact and may play an important role of colon cancer metastasis. Citation Format: Hidehiko Takigawa, Yasuhiko Kitadai, Toshio Kuwai, Ryo Yuge, Shinji Tanaka, Kazuaki Chayama. Mesenchymal stem cells promote epithelial-mesenchymal transition of colon cancer cells via direct cell-to-cell contact [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4341. doi:10.1158/1538-7445.AM2017-4341