Abstract
Abstract Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to contribute to the formation of tumor stroma. We reported recently that in an orthotopic nude mouse model of human colon cancer, MSCs migrated to tumor stroma, where they differentiated into carcinoma-associated fibroblast (CAF)-like cells and promoted tumor growth and metastasis. However, the molecular mechanisms of this phenomenon have not been elucidated. We performed microarray analysis of gene expression in KM12SM cells and found that expression of fibronectin (FN) mRNA was increased markedly by direct co-culture of KM12SM cells with MSCs. FN, a glycoprotein in extracellular matrix and also a maker of epithelial-mesenchymal transition (EMT), has been implicated in the development of several types of human cancer. Many reports indicate that EMT is an important step during the cascade of tumor progression. However, the potential role of FN in carcinogenesis is not fully elucidated. We examined FN expression in surgical specimens of human colon cancer and colon adenoma by immunohistochemistry. A total of 87 tumors were analyzed. Levels of FN expression in tumor cells correlated with disease stage, and FN immunoreactivity was detected in invasive cancers, especially at the invasive edge, but less in mucosal cancers or adenomas. Furthermore, in an orthotopic nude mouse model of colon cancer, mRNA expression levels of FN were shown to be higher in the tumors produced by KM12SM cells mixed with MSCs than in the tumors produced by KM12SM cells alone.These findings suggest that the interaction between cancer cells and MSCs recruited into tumor stroma may play a role in tumor growth and metastasis via induction of FN expression in invasive colon cancer. Citation Format: Kei Shinagawa, Yasuhiko Kitadai, Yuichiro Tanaka, Ryo Yuge, Mieko Onoyama, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama. Interaction between bone marrow-derived mesenchymal stem cells and tumor cells induces expression of fibronectin in human colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 180. doi:10.1158/1538-7445.AM2014-180
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