Abstract
Abstract Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor site. Because of this feature, they are currently being used in preclinical models and in clinical trials as potential vehicles for delivery of targeted anti-cancer therapies. Clinical applications of MSC however, require a deeper understanding of their biology and, in particular, of their interaction with cancer cells. In this study we have investigated the effects mediated by human bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC induced upregulation of epithelial-to-mesenchymal (EMT)-related genes and downregulation of E-cadherin in tumor cells. These effects required cell-to-cell contact and were mediated by expression of surface-bound TGF-β, induced in MSC upon coculture with tumor cells. CRC cells exposed to MSC formed larger tumor masses in vivo, characterized by higher vessel density and increased mesenchymal marker expression, and displayed enhanced invasive capacity. Thus, by promoting cell expansion, EMT-related phenomena and tumor angiogenesis, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. These findings raise concerns regarding the safety of MSC administration for clinical purposes in patients with cancer. Citation Format: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Nunzia Amatruda, Francesca Amicarella, Dennis Pfaff, Brynn Kvinlaug, Chiara Bocelli-Tyndall, Ivan Martin, Therese J. Resink, Luigi M. Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2013-1476
Published Version
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