Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment.

Autor: Szabo PM; Bristol Myers Squibb, Princeton, NJ, USA.; Fate Therapeutics, San Diego, CA, USA., Vajdi A; Dana-Farber Cancer Institute, Boston, MA, USA.; Merck & Co., Inc., Kenilworth, NJ, USA., Kumar N; Bristol Myers Squibb, San Diego, CA, USA. Namit.kumar@bms.com., Tolstorukov MY; Dana-Farber Cancer Institute, Boston, MA, USA., Chen BJ; Bristol Myers Squibb, Cambridge, MA, USA., Edwards R; Bristol Myers Squibb, Princeton, NJ, USA.; Daiichi Sankyo, Inc., Princeton, NJ, USA., Ligon KL; Dana-Farber Cancer Institute, Boston, MA, USA., Chasalow SD; Bristol Myers Squibb, Princeton, NJ, USA., Chow KH; Dana-Farber Cancer Institute, Boston, MA, USA., Shetty A; Dana-Farber Cancer Institute, Boston, MA, USA., Bolisetty M; Bristol Myers Squibb, Princeton, NJ, USA., Holloway JL; Bristol Myers Squibb, Seattle, WA, USA., Golhar R; Bristol Myers Squibb, Princeton, NJ, USA., Kidd BA; Bristol Myers Squibb, Redwood City, CA, USA., Hull PA; Bristol Myers Squibb, Redwood City, CA, USA., Houser J; Bristol Myers Squibb, Redwood City, CA, USA., Vlach L; Bristol Myers Squibb, Redwood City, CA, USA.; Vanderbilt University, Nashville, TN, USA., Siemers NO; Bristol Myers Squibb, Princeton, NJ, USA.; Fiveprime Group, Monterey, CA, USA., Saha S; Bristol Myers Squibb, Princeton, NJ, USA.; Centessa Pharmaceuticals, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Feb 21; Vol. 13 (1), pp. 3051. Date of Electronic Publication: 2023 Feb 21.
DOI: 10.1038/s41598-023-28480-9
Abstrakt: Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several tumor types to identify the source of EMT gene expression signals and a potential mechanism of resistance to immuno-oncology treatment. Across tumor types, EMT-related gene expression was strongly associated with expression of stroma-related genes. Based on RNA sequencing of multiple patient-derived xenograft models, EMT-related gene expression was enriched in the stroma versus parenchyma. EMT-related markers were predominantly expressed by cancer-associated fibroblasts (CAFs), cells of mesenchymal origin which produce a variety of matrix proteins and growth factors. Scores derived from a 3-gene CAF transcriptional signature (COL1A1, COL1A2, COL3A1) were sufficient to reproduce association between EMT-related markers and disease prognosis. Our results suggest that CAFs are the primary source of EMT signaling and have potential roles as biomarkers and targets for immuno-oncology therapies.
(© 2023. The Author(s).)
Databáze: MEDLINE
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