Direct contacts with colon cancer cells regulate the differentiation of bone marrow mesenchymal stem cells into tumor associated fibroblasts |
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Authors: | Yanan Peng Zongwei Li Peng Yang Ian P Newton Hua Ren Lichao Zhang Haili Wu Zhuoyu Li |
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Institution: | 1. Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China;2. College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China;3. Division of Cell & Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD15EH, Scotland, UK;4. Shanxi College of Traditional Chinese Medicine and Western Medicine Hospital, Taiyuan 030013, China |
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Abstract: | 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. |
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Keywords: | BMSCs bone marrow-derived mesenchymal stem cells TAF tumor-associated fibroblast α-SMA α-smooth muscle actin MSCs mesenchymal stem cells FBS fetal bovine serum PFA paraformaldehyde SE standard error GFP green fluorescent protein BMMSCs murine bone marrow-derived mesenchymal stem cells p-Akt the phosphorylated form of AKT p-Smad2/3 the phosphorylated form of Smad2/3 |
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