Role of stromal cells-mediated Notch-1 in the invasion of T-ALL cells.

Extra-medullary infiltration is still one of the main causes of recurrence and treatment failure of T-cell acute lymphoblastic leukemia (T-ALL). Intensive studies revealed that Notch pathway plays an important role in the invasion of tumor cells. Notch pathway can be triggered by binding of Notch receptors on T-ALL cells to their ligands on bone marrow stromal cells (BMSCs), which contributes to the development of T-ALL. However, the effect and molecular mechanisms of BMSCs in invasion of T-ALL cells remain unclear. To explore the effect of Notch-1 on the invasiveness of T-ALL cells, we co-cultured T-ALL cells with BMSCs (from healthy donors)/BMSCs(⁎) (from newly diagnosed T-ALL patients). The results demonstrated that BMSCs/BMSCs(⁎) promoted invasion of T-ALL cells through activating Notch-1 signaling. In particular, T-ALL cells showed a higher invasive potential in the presence of BMSCs(⁎) than BMSCs. Knockdown of Notch-1 prevented the positive effect of stromal cells-mediated invasion. Our study also showed that BMSCs/BMSCs(⁎)-induced Notch-1 activation increased the expression of matrix metalloprote inase-2 (MMP-2) and matrix metalloprote inase-9 (MMP-9), which increased invasiveness. These results provided theoretical and laboratory basis for the prevention and treatment of extra-medullary infiltration of T-ALL cells.