MICROSCOPY Vol.46▶No.2 2011
â– Feature Articles: Tumor Initiating Cells and Their Regulation

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

Shuho Semba

Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine

Abstract: 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.

Key words: bone marrow-derived mesenchymal stem cells (BM-MSC), cancer stem cells, cancer-associated fibroblast (CAF), WNT5A, TGF-β