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

Mark J. Schliekelman, Chad J. Creighton, Brandi N. Baird, Yulong Chen, Priyam Banerjee, Neus Bota-Rabassedas, Young Ho Ahn, Jonathon D. Roybal, Fengju Chen, Yiqun Zhang, Dhruva K Mishra, Min P Kim, Xin Liu, Barbara Mino, Pamela Villalobos, Jaime Rodriguez-Canales, Carmen Behrens, Ignacio Wistuba, Samir M. Hanash, Jonathan M. Kurie

Research output: Contribution to journalArticle

16 Scopus citations

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 Kras(G12D)-driven lung adenocarcinoma (Kras(LA1)), 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 Kras(LA1) 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.

Original languageEnglish (US)
Pages (from-to)6478
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Jul 25 2017

Keywords

  • Journal Article

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