Human Gene Set: MISHRA_CARCINOMA_ASSOCIATED_FIBROBLAST_DN


Standard name MISHRA_CARCINOMA_ASSOCIATED_FIBROBLAST_DN
Systematic name M4577
Brief description Top genes down-regulated in mesenchyme stem cells (MSC) grown in a tumor conditioned medium, which leads to carcinoma-associated fibroblast phenotype.
Full description or abstract Carcinoma-associated fibroblasts (CAF) have recently been implicated in important aspects of epithelial solid tumor biology, such as neoplastic progression, tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from nonneoplastic tissue have been well defined. In this study, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs, including sustained expression of stromal-derived factor-1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo coimplantation model, and expression of myofibroblast markers, including alpha-smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cell growth as efficiently as hMSCs cultured in TCM nor do they show increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM-exposed hMSCs and CAFs. Taken together, these data suggest that hMSCs are a source of CAFs and can be used in the modeling of tumor-stroma interactions. To our knowledge, this is the first report showing that hMSCs become activated and resemble carcinoma-associated myofibroblasts on prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18519693   Authors: Mishra PJ,Mishra PJ,Humeniuk R,Medina DJ,Alexe G,Mesirov JP,Ganesan S,Glod JW,Banerjee D
Exact source p. 4335: Top 25 (of 47) down-regulated genes
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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