Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis
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...
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Nature Portfolio
2017
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oai:doaj.org-article:b98c31b4556442fb996362e7c46fd3c22021-12-02T12:31:53ZThy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis10.1038/s41598-017-06922-52045-2322https://doaj.org/article/b98c31b4556442fb996362e7c46fd3c22017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06922-5https://doaj.org/toc/2045-2322Abstract 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.Mark J. SchliekelmanChad J. CreightonBrandi N. BairdYulong ChenPriyam BanerjeeNeus Bota-RabassedasYoung-Ho AhnJonathon D. RoybalFengju ChenYiqun ZhangDhruva K. MishraMin P. KimXin LiuBarbara MinoPamela VillalobosJaime Rodriguez-CanalesCarmen BehrensIgnacio I. WistubaSamir M. HanashJonathan M. KurieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q |
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Medicine R Science Q 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 I. Wistuba Samir M. Hanash Jonathan M. Kurie Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| description |
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. |
| format |
article |
| author |
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 I. Wistuba Samir M. Hanash Jonathan M. Kurie |
| author_facet |
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 I. Wistuba Samir M. Hanash Jonathan M. Kurie |
| author_sort |
Mark J. Schliekelman |
| title |
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| title_short |
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| title_full |
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| title_fullStr |
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| title_full_unstemmed |
Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis |
| title_sort |
thy-1+ cancer-associated fibroblasts adversely impact lung cancer prognosis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b98c31b4556442fb996362e7c46fd3c2 |
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