Gene Set: ZHONG_SECRETOME_OF_LUNG_CANCER_AND_ENDOTHELIUM

Standard name ZHONG_SECRETOME_OF_LUNG_CANCER_AND_ENDOTHELIUM
Systematic name M1686
Brief description Proteins secreted in co-culture of LKR-13 tumor cells (non-small cell lung cancer, NSCLC) and MEC stroma cells (endothelium).
Full description or abstract Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed stromal cells) that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18757440   Authors: Zhong L,Roybal J,Chaerkady R,Zhang W,Choi K,Alvarez CA,Tran H,Creighton CJ,Yan S,Strieter RM,Pandey A,Kurie JM
Exact source Table 1S: MEC/LKR-13 co-cultures
Related gene sets (show 2 additional gene sets from the source publication)

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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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