Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model. Academic Article uri icon

Overview

MeSH

  • Algorithms
  • Animals
  • Autocrine Communication
  • Bone Marrow Cells
  • Carcinoma, Non-Small-Cell Lung
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells
  • Interleukin-6
  • Lung
  • Lung Neoplasms
  • Mice
  • Paracrine Communication
  • Receptors, Interleukin-6
  • Sequence Analysis, RNA
  • Transcriptome
  • Tumor Microenvironment
  • ras Proteins

MeSH Major

  • Gene Expression Profiling
  • Stromal Cells

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. Copyright ¬© 2015 The Authors. Published by Elsevier Inc. All rights reserved.

publication date

  • February 24, 2015

has subject area

  • Algorithms
  • Animals
  • Autocrine Communication
  • Bone Marrow Cells
  • Carcinoma, Non-Small-Cell Lung
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells
  • Gene Expression Profiling
  • Interleukin-6
  • Lung
  • Lung Neoplasms
  • Mice
  • Paracrine Communication
  • Receptors, Interleukin-6
  • Sequence Analysis, RNA
  • Stromal Cells
  • Transcriptome
  • Tumor Microenvironment
  • ras Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.01.040

PubMed ID

  • 25704820

Additional Document Info

start page

  • 1187

end page

  • 1201

volume

  • 10

number

  • 7