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Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Title
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis
Authors
Schliekelman M.J.Creighton C.J.Baird B.N.Chen Y.Banerjee P.Bota-Rabassedas N.Ahn Y.-H.Roybal J.D.Chen F.Zhang Y.Mishra D.K.Kim M.P.Liu X.Mino B.Villalobos P.Rodriguez-Canales J.Behrens C.Wistuba I.I.Hanash S.M.Kurie J.M.
Ewha Authors
안영호
SCOPUS Author ID
안영호scopus
Issue Date
2017
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 7, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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 α-smooth muscle actin (αSMA), 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. © 2017 The Author(s).
DOI
10.1038/s41598-017-06922-5
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의과대학 > 의학과 > Journal papers
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