Bone Marrow-Derived Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Gastric Cancer Stem Cells

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  • Semba Shuho
    Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine

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Other Title
  • 骨髄由来間葉系幹細胞によるがん幹細胞性再獲得機構
  • コツズイ ユライ カンヨウケイ カンサイボウ ニ ヨル ガン カンサイボウセイ サイカクトク キコウ

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Abstract

<p>In this study, we investigated the impact of UE6E7T-12 bone marrow-derived mesenchymal stem cells (BM-MSCs) on the proliferation and cluster formation of gastric carcinoma (GC)-derived MKN-7 cells. Interestingly, co-culture with UE6E7T-12 BM-MSCs increased the population of CD133+ MKN-7 cells in vitro and co-implantation of MKN-7 cells and UE6E7T-12 BM-MSCs in mice resulted in subcutaneous tumors in vivo, suggesting BM-MSCs’ function in the restoration of cancer stem cells (CSCs). By a differential analysis of gene expression profiles, we identified that co-incubation of MKN-7 cells and UE6E7T-12 BM-MSCs induced WNT5A expression in MKN-7 cells and TGF-β1 expression in UE6E7T-12 BM-MSCs, respectively. Of note, WNT5A and TGF-β1 independently enlarged the population of CD133+ MKN-7 cells, even in the absence of co-culture with UE6E7T-12 BM-MSCs. In human diffuse-type GC tissues, recruitment of CD271+ BM-MSC was detected in the tumor stroma and GC cells showed frequent positivity against WNT5A, TGF-β type I receptor and CD133. These findings suggest that BM-MSCs provide an advantageous microenvironment for cancer progression by supporting the re-acquisition and maintenance of CSCs. BM-MSC-mediated activations of the WNT and TGF-β signaling pathways may be attractive therapeutic targets for blocking the evolution of GC cells.</p>

Journal

  • KENBIKYO

    KENBIKYO 46 (2), 89-94, 2011-06-30

    The Japanese Society of Microscopy

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