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

Mele, Valentina; Basso, Camilla; Governa, Valeria; Glaus Garzon, Jesus F.; Muraro, Manuele G.; Däster, Silvio; Nebiker, Christian A.; Mechera, Robert; Bolli, Martin; Schmidt, Alexander; Geiger, Roger; Spagnoli, Giulio C; Christoforidis, Dimitri; Majno, Pietro E.; Borsig, Lubor; Iezzi, Giandomenica

doi:10.3390/cancers14082024

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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

2022

Published in:

Cancers. - 2022, vol. 14, p. 2024

Tumor-associated stromal cells

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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