p27 modulates tropism of mesenchymal stem cells toward brain tumors.

Mesenchymal stem cells (MSCs) have inherent tumor-tropic properties in the brain and seem to be a useful tool for cellular therapy for brain tumors. However, the mechanisms involved in MSC migration are not fully understood. The tumor suppressor p27, an inhibitor of cyclin-dependent kinase complexes, not only plays a crucial role in cell cycle regulation but also has cell cycle-independent functions, such as differentiation and migration of cells. In fact, p27 has been alternatively reported to inhibit or stimulate cell migration in cells of different types. Therefore, in the present study, we investigated whether p27 is involved in the tumor-tropic activity of MSCs using MSCs from p27-null mice. It was found that p27-/- MSCs showed a decreased motility in the wound healing assay and displayed increased numbers of stress fibers. To compare the in vivo migratory activity of p27-/- and p27+/+ MSCs toward glioma, we injected C6 glioma cells into one side of the mouse brain and BrdU-labeled p27-/- or p27+/+ MSCs into the other side. Significantly fewer labeled p27-/- MSCs were observed in the tumor area compared with p27+/+ MSCs. The present study suggests that p27 works as a stimulator of the in vitro and in vivo migration process of MSCs toward tumors. These findings are important when the efficacy of stem cell-based strategies for glioma therapy is considered.