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Publication : Thy-1<sup>+</sup> Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis.

First Author  Schliekelman MJ Year  2017
Journal  Sci Rep Volume  7
Issue  1 Pages  6478
PubMed ID  28744021 Mgi Jnum  J:257292
Mgi Id  MGI:5925835 Doi  10.1038/s41598-017-06922-5
Citation  Schliekelman MJ, et al. (2017) Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis. Sci Rep 7(1):6478
abstractText  Cancer-associated fibroblasts (CAFs) regulate diverse intratumoral biological programs and can promote or inhibit tumorigenesis, but those CAF populations that negatively impact the clinical outcome of lung cancer patients have not been fully elucidated. Because Thy-1 (CD90) marks CAFs that promote tumor cell invasion in a murine model of KrasG12D-driven lung adenocarcinoma (KrasLA1), here we postulated that human lung adenocarcinomas containing Thy-1+ CAFs have a worse prognosis. We first examined the location of Thy-1+ CAFs within human lung adenocarcinomas. Cells that co-express Thy-1 and alpha-smooth muscle actin (alphaSMA), a CAF marker, were located on the tumor periphery surrounding collectively invading tumor cells and in perivascular regions. To interrogate a human lung cancer database for the presence of Thy-1+ CAFs, we isolated Thy-1+ CAFs and normal lung fibroblasts (LFs) from the lungs of KrasLA1 mice and wild-type littermates, respectively, and performed global proteomic analysis on the murine CAFs and LFs, which identified 425 proteins that were differentially expressed. Used as a probe to identify Thy-1+ CAF-enriched tumors in a compendium of 1,586 lung adenocarcinomas, the presence of the 425-gene signature predicted a significantly shorter survival. Thus, Thy-1 marks a CAF population that adversely impacts clinical outcome in human lung cancer.
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