['In tumors, vascular endothelial growth factor-A (VEGF-A) stimulates angiogenesis and vascular permeability by activating the tyrosine kinase receptor-2 (VEGFR-2 or KDR/Flk-1) and-1 (VEGFR-1 or Flt-1).', 'The distribution and function of VEGF homologs and their receptors on bone marrow plasma cells, endothelial cells, and other stromal cells (residual stromal cells) were examined in patients with multiple myeloma (MM).', 'Plasma cells secrete VEGF-A (and VEGF-B, VEGF-C and VEGF-D, albeit marginally) into their conditioned medium (CM). CM VEGF-A stimulates proliferation and chemotaxis in endothelial cells (both being mandatory for angiogenesis) via VEGF receptor-2 (VEGFR-2), and in residual stromal cells via the VEGFR-1. Residual stromal cells secrete VEGF-C and VEGF-D, but little of the other homologs. Their CM VEGF-C and VEGF-D increase in response to plasma cell CM and trigger plasma cell proliferation via VEGFR-3. Proliferation in all cell types parallels VEGFR and extracellular signal-regulated protein kinase-2 (ERK-2) phosphorylation. The homologs and receptors are weakly or inconstantly expressed in patients with monoclonal gammopathies of undetermined significance or vitamin B12/iron deficiency anemias.'] Does a paracrine loop in the vascular endothelial growth factor pathway trigger tumor angiogenesis and growth in multiple myeloma?