title: Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Jianting
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Dingcheng
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Durrans
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Seongho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Sharrell B
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Pathology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.affiliation: Ansary Stem Cell Institute and Department of Genetic Medicine, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.affiliation: Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Altorki
authors.affiliation: Department of Pathology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA; Methodist Cancer Center, Houston Methodist Hospital, 6650 Fannin Street, Houston, TX 77030, USA. Electronic address: stwong@houstonmethodist.org.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
authors.affiliation: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, 525 East 68(th) Street, New York, NY 10065, USA. Electronic address: vim2010@med.cornell.edu.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mittal
mesh_terms: D000465:Algorithms; D000818:Animals; D019898:Autocrine Communication; D001854:Bone Marrow Cells / Q000166:cytology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019899:Paracrine Communication; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D017423:Sequence Analysis, RNA; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome; D059016:Tumor Microenvironment; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D018631:ras Proteins