Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies

Vascular endothelial growth factor (VEGF) plays an important role in angiog enesis by acting as a potent inducer of vascular permeability as well as se rving as a specific endothelial cell mitogen, The importance of angiogenic factors such as VEGF, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. We examined the ex pression of mRNA and protein for VEGF in 12 human hematopoietic tumor cell lines, representing multiple lineages and diseases, including leukemia, lym phoma, and multiple myeloma, Our results revealed that VEGF message was exp ressed in these cells and that the corresponding protein was secreted into the extracellular environment. Five of the 12 cell lines were also found to express the Flt-1 receptor for VEGF: at a moderate to strong level, sugges ting an autocrine pathway, When human vascular endothelial cells were expos ed to recombinant human VEGF, there was an increase in the mRNA for several hematopoietic growth factors including macrophage colony-stimulating facto r, granulocyte colony-stimulating factor and interleukin 6, Plasma cells in the bone marrow from patients diagnosed with multiple myeloma were found t o express VEGF, whereas both the Flt-1 and KDR high affinity VEGF receptors were observed to be markedly elevated in the normal bone marrow myeloid an d monocytic cells surrounding the tumor, These data raise the possibility t hat VEGF map play a role in the growth of hematopoietic neoplasms such as m ultiple myeloma through either a paracrine or an autocrine mechanism.