Notch1 produces a deregulation of CXCR4/SDF-1 chemokine signaling in multiple myeloma cells (149.12)

Abstract

Notch deregulation occurs in several solid and hematopoietic tumors. Recently, the Notch receptor oncogenic role has been shown to be critical in multiple myeloma (MM) which frequently displays deregulation of the Notch ligand, Jagged2. MM is a malignant disorder of Ig-secreting plasma cells which accumulate in the bone marrow and cause bone lesions through stimulation of osteoclast activity. Several chemokines and their receptors (CRs) are critical in MM progression. Particularly, the axis SDF1-a/CXCR4 promotes MM cell growth, recruiting in the bone marrow compartment, apoptosis resistance, angiogenesis and osteolysis. This work aims to explore the effects of the Notch oncogenic pathway on the expression and function of a number of CRs and correspondent ligands which display a critical role in MM. Our results indicate that Notch pathway plays a regulative role on the expression and function of CXCR4/SDF-1α axis in different MM cell lines including RPMI-8226, KMS-12 and OPM-2.