Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.

Abstract

Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.