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

Mele, V. and Muraro, M. G. and Calabrese, D. and Pfaff, D. and Amatruda, N. and Amicarella, F. and Kvinlaug, B. and Bocelli-Tyndall, C. and Martin, I. and Resink, T. J. and Heberer, M. and Oertli, D. and Terracciano, L. and Spagnoli, G. C. and Iezzi, G.. (2014) Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-beta. International journal of cancer, Vol. 134, H. 11. pp. 2583-2594.

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Official URL: http://edoc.unibas.ch/dok/A6338108

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Abstract

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-beta 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. (c) 2013 Wiley Periodicals, Inc.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tissue Engineering (Martin)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunotherapy (Iezzi)
UniBasel Contributors:Spagnoli, Giulio C. and Resink, Thérèse J. and Heberer, Michael and Martin, Ivan and Iezzi, Giandomenica
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Alan R. Liss
ISSN:0020-7136
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:06 Feb 2015 09:59

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