Journal
CELL REPORTS
Volume 10, Issue 7, Pages 1187-1201Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.01.040
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Funding
- Neuberger Berman Foundation Lung Cancer Center funds
- Arthur and Myra Mahon Donor-Advised Fund
- Claiborne and Art Ortenberg Foundation
- R. & M. Goldberg Family Foundation
- P. & C. Collins Fund
- William and Shelby Modell Family Foundation Trust
- Division of Thoracic Surgery
- John S. Dunn Research Foundation [NIH U54CA149196, NIH R01 CA121225]
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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-smallcell 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 maycomplement conventional anti-cancer treatments.
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