Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model
Hyejin Choi,
Jianting Sheng,
Dingcheng Gao,
Fuhai Li,
Anna Durrans,
Seongho Ryu,
Sharrell B. Lee,
Navneet Narula,
Shahin Rafii,
Olivier Elemento,
Nasser K. Altorki,
Stephen T.C. Wong,
Vivek Mittal
Affiliations
Hyejin Choi
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Jianting Sheng
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA
Dingcheng Gao
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Fuhai Li
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA
Anna Durrans
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Seongho Ryu
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Sharrell B. Lee
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Navneet Narula
Department of Pathology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Shahin Rafii
Ansary Stem Cell Institute and Department of Genetic Medicine, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Olivier Elemento
Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Nasser K. Altorki
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Stephen T.C. Wong
Department of Pathology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Vivek Mittal
Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68th Street, New York, NY 10065, USA
Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.
