Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells
(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.
(Less)
- author
- organization
- publishing date
- 2022-04-01
- 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
-
- pmid:35454931
- scopus:85128567287
- 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
- 2024-09-19 19:07:28
@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}}, }