Up-regulation of connexin-43 expression in bone marrow mesenchymal stem cells plays a crucial role in adhesion and migration of multiple myeloma cells

Abstract

Multiple myeloma (MM) cells accumulate mainly in the bone marrow (BM) and are closely related to the BM microenvironment. Connexin-43 (Cx43) is the main connexin present in bone marrow mesenchymal stem cells (BMSCs). We found that normal BMSCs expressed a lower level of Cx43 than those derived from patients with MM. Cx43 expression in BMSCs was up-regulated at both the gene and protein level, and gap junction-mediated intercellular communication was improved in BMSCs after co-culture with RPMI 8226 cells. The gap junction blocker 18α-glycyrrhetinic acid (18α-GA) inhibited the adherence of MM cells to BMSCs. Treatment with 18α-GA decreased stromal cell-derived factor-1α (SDF-1α) secretion by BMSCs and inhibited the migration of MM cells induced by BMSCs. These results suggest that alteration of Cx43 expression in BMSCs is involved in the interactions of MM cells with the BM environment and plays a crucial role in the adhesion and migration of MM cells.

Keywords::

• Multiple myeloma
• mesenchymal stem cells
• connexin-43
• stromal cell-derived factor-1α
• adhesion
• migration

Potential conflict of interest

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This study was supported by grants from the National Natural Science Foundation of China (NFSC, Grant Nos. 80171934, 81272631, 81172256) and the Graduate research and Innovation Projects of Jiangsu Province (No CXLX12-0835).