Journal article

Identification of TPM2 and CNN1 as novel prognostic markers in functionally characterized human colon cancer-associated stromal cells

  • Mele, Valentina ORCID Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland
  • Basso, Camilla Laboratory for Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland - Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Governa, Valeria ORCID Department of Clinical Sciences Lund, Section of Oncology, Lund University, Lund, Sweden
  • Glaus Garzon, Jesus F. Institute of Physiology, University of Zürich, Zürich, Switzerland
  • Muraro, Manuele G. ORCID Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland
  • Däster, Silvio ORCID Department of General Surgery, University Hospital Basel, Basel, Switzerland
  • Nebiker, Christian A. Department of General Surgery, University Hospital Basel, Basel, Switzerland
  • Mechera, Robert ORCID Department of General Surgery, University Hospital Basel, Basel, Switzerland
  • Bolli, Martin Department of Visceral Surgery, Clarunis-University Center for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, Basel, Switzerland;
  • Schmidt, Alexander Proteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland
  • Geiger, Roger ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Spagnoli, Giulio C Institute of Translational Pharmacology, National Research Council, Rome, Italy
  • Christoforidis, Dimitri Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Surgery, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
  • Majno, Pietro E. Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Surgery, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
  • Borsig, Lubor ORCID Institute of Physiology, University of Zürich, Zürich, Switzerland
  • Iezzi, Giandomenica Laboratory for Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland - Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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  • 2022
Published in:
  • Cancers. - 2022, vol. 14, p. 2024
English Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial–mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.
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Language
  • English
Classification
Medicine
License
CC BY
Open access status
gold
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Persistent URL
https://susi.usi.ch/usi/documents/322801
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