학술논문
Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment.
Document Type
Article
Author
Szabo, Peter M.; Vajdi, Amir; Kumar, Namit; Tolstorukov, Michael Y.; Chen, Benjamin J.; Edwards, Robin; Ligon, Keith L.; Chasalow, Scott D.; Chow, Kin-Hoe; Shetty, Aniket; Bolisetty, Mohan; Holloway, James L.; Golhar, Ryan; Kidd, Brian A.; Hull, Philip Ansumana; Houser, Jeff; Vlach, Logan; Siemers, Nathan O.; Saha, Saurabh
Source
Subject
*FIBROBLASTS
*TUMOR microenvironment
*EPITHELIAL-mesenchymal transition
*GENE expression
*RNA sequencing
*GROWTH factors
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Language
ISSN
2045-2322
Abstract
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. [ABSTRACT FROM AUTHOR]