CD138-negative myeloma cells regulate mechanical properties of bone marrow stromal cells through SDF-1/CXCR4/AKT signaling pathway

article Stiffness CD138-negative SDF-1/CXCR4 AKT As the second most prevalent hematologic malignancy, multiple myeloma (MM) remains incurable and relapses due to intrinsic or acquired drug resistance. Therefore, new therapeutic strategies that target molecular mecha- nisms responsible for drug resistance are attractive. Interactions of tumor cells with their surrounding microen- vironment impact tumor initiation, progression and metastasis, as well as patient prognosis. This cross-talk is bidirectional. Tumor cells can also attract or activate tumor-associated stromal cells by releasing cytokines to fa- cilitate their growth, invasion and metastasis. The effect of myeloma cells on bone marrow stromal cells(BMSCs) hasnotbeenwellstudied.Inourstudy,we foundthathigherstiffnessofBMSCswasnotaunique characteristicof BMSCs from MM patients (M-BMSCs). BMSCs from MGUS (monoclonal gammopathy of undetermined signifi- cance) patients were also stiffer than the BMSCs from healthy volunteers (N-BMSCs). The stiffness of M-BMSCs was enhanced when cocultured with myeloma cells. In contrast, no changes were seen in myeloma cell- primed MGUS- and N-BMSCs. Interestingly, our data indicated that CD138 � myeloma cells, but not CD138 +