Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-ß
| Autor: | Daniel Oertli, Chiara Bocelli-Tyndall, Francesca Amicarella, Diego Calabrese, Valentina Mele, Dennis Pfaff, Manuele G. Muraro, Thérèse J. Resink, Brynn Kvinlaug, Giandomenica Iezzi, Luigi Terracciano, Michael Heberer, Giulio C. Spagnoli, Ivan Martin, Nunzia Amatruda |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Fluorescent Antibody Technique Apoptosis Cell Communication Mice SCID Mice 0302 clinical medicine Bone Marrow Cell Movement Mice Inbred NOD Transforming Growth Factor beta Cells Cultured Skin 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction EMT Cadherins Flow Cytometry medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cytokines Chemokines Colorectal Neoplasms Epithelial-Mesenchymal Transition Stromal cell Blotting Western surface-bound TGF-β colorectal cancer Real-Time Polymerase Chain Reaction MSC 03 medical and health sciences Downregulation and upregulation In vivo Cell Adhesion medicine Animals Humans Neoplasm Invasiveness RNA Messenger Epithelial–mesenchymal transition Cell Proliferation 030304 developmental biology Cell Membrane Mesenchymal stem cell Mesenchymal Stem Cells Transforming growth factor beta Fibroblasts Molecular biology Cancer cell biology.protein Cancer research Bone marrow Cancer Cell Biology |
| Zdroj: | International journal of cancer. Journal international du cancer International Journal of Cancer. Journal International du Cancer |
| DOI: | 10.1002/ijc.28598 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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