Direct contacts with colon cancer cells regulate the differentiation of bone marrow mesenchymal stem cells into tumor associated fibroblasts

• Published in: Biochemical and biophysical research communications 2014-08, Vol.451 (1), p.68-73
• Main Authors: Peng, Yanan, Li, Zongwei, Yang, Peng, Newton, Ian P., Ren, Hua, Zhang, Lichao, Wu, Haili, Li, Zhuoyu
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Bone Marrow Cells - cytology; Calcium-Binding Proteins - metabolism; Cell Communication; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Colon cancer cell; Colonic Neoplasms - pathology; Differentiation; Fibroblasts - pathology; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - metabolism; Mesenchymal stem cell; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Notch signaling pathway; Receptors, Notch - metabolism; Serrate-Jagged Proteins; Signal Transduction; Smad Proteins - metabolism; TGF-β/Smad signaling pathway; Transforming Growth Factor beta - metabolism; Tumor Microenvironment; Tumor-associated fibroblast
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.07.074

•Colon cancer cells induce differentiation of BMSCs into TAFs by cell–cell contacts.•Notch–Jagged1 signaling is involved in differentiation of BMSCs into TAFs.•Notch mediates BMSCs–TAFs transition via downstream TGF-β/Smad signaling pathway. Tumor–stroma interactions are referred to as essential events in tumor progression. There has been growing attention that bone marrow-derived mesenchymal stem cells (BMSCs) can travel to tumor stroma, where they differentiate into tumor-associated fibroblast (TAF)-like cells, a predominant tumor-promoting stromal cell. However, little is definitively known about the contributors for this transition. Here, using an in vitro direct co-culture model of colon cancer cells and BMSCs, we identify that colon cancer cells can induce adjoining BMSCs to exhibit the typical characteristic of TAFs, with increased expression of α-smooth muscle actin (α-SMA). Importantly, the present data also reveals that activated Notch signaling mediates transformation of BMSCs to TAFs through the downstream TGF-β/Smad signaling pathway.