Identification of TPM2 and CNN1 as novel prognostic markers in functionally characterized human colon cancer-associated stromal cells
Informazioni aggiuntive
Autori
Mele V.,
Basso C.,
Governa V.,
Glaus Garzon J. F.,
Muraro M. G.,
Däster S.,
Nebiker C. A.,
Mechera R.,
Bolli M.,
Schmidt A.,
Geiger R.,
Spagnoli G. C.,
Christoforidis D.,
Majno-Hurst P.,
Borsig L.,
Iezzi G.
Tipo
Articolo pubblicato in rivista scientifica
Anno
2022
Lingua
Inglese
Sommario
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.
Parole chiave
Colon cancer, Tumor-associated stromal cells, Proteomics, Prognostic markers, TPM2, CNN1
Periodico
Cancers
Volume
14
Pagine (o numero dell’articolo)
2024
Diffusione
Licenza
CC BY
Visibilità
Pubblico
Status open access
Gold
