VEGF-mediated proliferation and migration of MM cells.

VEGF stimulates proliferation and migration of MM cells in a paracrine and autocrine pathway. Within the bone marrow, VEGF is produced by both MM cells and BMSCs. IL-6 secreted by BMSCs enhances the production and secretion of VEGF by MM cells. Conversely, VEGF secreted by MM cells enhances IL-6 production by BMSCs. Binding of MM cells to BMSCs increases both IL-6 and VEGF secretion. Besides stimulating angiogenesis in the BM, VEGF directly triggers cell growth and migration of MM cells via the Raf-1–MEK-1–ERK cascade and a PKC-dependent ERK-independent pathway, respectively.