Mesenchymal stromal cells induce epithelial‐to‐mesenchymal transition in human colorectal cancer cells through the expression of surface‐bound TGF‐β

Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor sites, where they can integrate into the tumor‐associated stroma. However, molecular mechanisms and outcome of their interaction with cancer cells have not been fully clar...

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Veröffentlicht in:International journal of cancer 2014-06, Vol.134 (11), p.2583-2594
Hauptverfasser: Mele, Valentina, Muraro, Manuele G., Calabrese, Diego, Pfaff, Dennis, Amatruda, Nunzia, Amicarella, Francesca, Kvinlaug, Brynn, Bocelli‐Tyndall, Chiara, Martin, Ivan, Resink, Therese J., Heberer, Michael, Oertli, Daniel, Terracciano, Luigi, Spagnoli, Giulio C., Iezzi, Giandomenica
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Sprache:eng
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Zusammenfassung:Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor sites, where they can integrate into the tumor‐associated stroma. However, molecular mechanisms and outcome of their interaction with cancer cells have not been fully clarified. In this study, we investigated the effects mediated by bone marrow‐derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC triggered epithelial‐to‐mesenchymal transition (EMT) in tumor cells in vitro, as indicated by upregulation of EMT‐related genes, downregulation of E‐cadherin and acquisition of mesenchymal morphology. These effects required cell‐to‐cell contact and were mediated by surface‐bound TGF‐β newly expressed on MSC upon coculture with tumor cells. In vivo tumor masses formed by MSC‐conditioned CRC cells were larger and characterized by higher vessel density, decreased E‐cadherin expression and increased expression of mesenchymal markers. Furthermore, MSC‐conditioned tumor cells displayed increased invasiveness in vitro and enhanced capacity to invade peripheral tissues in vivo. Thus, by promoting EMT‐related phenomena, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. What's new? Mesenchymal stem/stromal cells (MSCs) are recruited into tumor‐associated stroma, but their interactions with cancer cells are not fully understood. In this study, the authors found that MSCs can trigger epithelial‐to‐mesenchymal transition (EMT) of human colorectal cancer (CRC) cells via cell‐to‐cell contact. This phenomenon required membrane‐bound TGF‐beta, which was newly expressed by MSCs upon cross‐talk with tumor cells. These results reveal a novel mechanism by which MSCs can enhance the aggressiveness of tumor cells, and they suggest a potential new therapeutic target in CRC.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.28598