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Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Mele, Valentina ; Basso, Camilla ; Governa, Valeria LU ; Glaus Garzon, Jesus F. ; Muraro, Manuele G. ; Däster, Silvio ; Nebiker, Christian A. ; Mechera, Robert ; Bolli, Martin and Schmidt, Alexander , et al. (2022) In Cancers 14(8).
Abstract

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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CNN1, colon cancer, prognostic markers, proteomics, TPM2, tumor-associated stromal cells
in
Cancers
volume
14
issue
8
article number
2024
publisher
MDPI AG
external identifiers
  • scopus:85128567287
  • pmid:35454931
ISSN
2072-6694
DOI
10.3390/cancers14082024
language
English
LU publication?
yes
id
2e3e4404-a9b9-4b67-b4fc-92be437e50b3
date added to LUP
2022-07-06 14:01:36
date last changed
2024-06-27 11:23:47
@article{2e3e4404-a9b9-4b67-b4fc-92be437e50b3,
  abstract     = {{<p>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.</p>}},
  author       = {{Mele, Valentina and Basso, Camilla and Governa, Valeria and Glaus Garzon, Jesus F. and Muraro, Manuele G. and Däster, Silvio and Nebiker, Christian A. and Mechera, Robert and Bolli, Martin and Schmidt, Alexander and Geiger, Roger and Spagnoli, Giulio C. and Christoforidis, Dimitri and Majno, Pietro E. and Borsig, Lubor and Iezzi, Giandomenica}},
  issn         = {{2072-6694}},
  keywords     = {{CNN1; colon cancer; prognostic markers; proteomics; TPM2; tumor-associated stromal cells}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{8}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells}},
  url          = {{http://dx.doi.org/10.3390/cancers14082024}},
  doi          = {{10.3390/cancers14082024}},
  volume       = {{14}},
  year         = {{2022}},
}