Bellamy W T, Richter L, Frutiger Y, Grogan T M
Department of Pathology, University of Arizona, Tucson 85724, USA.
Cancer Res. 1999 Feb 1;59(3):728-33.
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by acting as a potent inducer of vascular permeability as well as serving 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 expression of mRNA and protein for VEGF in 12 human hematopoietic tumor cell lines, representing multiple lineages and diseases, including leukemia, lymphoma, and multiple myeloma. Our results revealed that VEGF message was expressed 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, suggesting an autocrine pathway. When human vascular endothelial cells were exposed to recombinant human VEGF, there was an increase in the mRNA for several hematopoietic growth factors including macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 6. Plasma cells in the bone marrow from patients diagnosed with multiple myeloma were found to 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 and monocytic cells surrounding the tumor. These data raise the possibility that VEGF may play a role in the growth of hematopoietic neoplasms such as multiple myeloma through either a paracrine or an autocrine mechanism.
血管内皮生长因子（VEGF）作为血管通透性的强效诱导剂以及特定的内皮细胞促有丝分裂原，在血管生成中发挥着重要作用。血管生成因子如VEGF的重要性，虽然在实体瘤中已明确确立，但在人类造血肿瘤中尚未完全阐明。我们检测了12种人类造血肿瘤细胞系中VEGF的mRNA和蛋白表达，这些细胞系代表多种谱系和疾病，包括白血病、淋巴瘤和多发性骨髓瘤。我们的结果显示，这些细胞中表达了VEGF信息，且相应蛋白分泌到细胞外环境中。还发现12种细胞系中的5种以中等至强水平表达VEGF的Flt-1受体，提示存在自分泌途径。当人血管内皮细胞暴露于重组人VEGF时，包括巨噬细胞集落刺激因子、粒细胞集落刺激因子和白细胞介素6在内的几种造血生长因子的mRNA有所增加。在诊断为多发性骨髓瘤的患者骨髓中的浆细胞被发现表达VEGF，而在肿瘤周围的正常骨髓髓系和单核细胞中观察到Flt-1和KDR高亲和力VEGF受体均显著升高。这些数据提示，VEGF可能通过旁分泌或自分泌机制在多发性骨髓瘤等造血肿瘤的生长中发挥作用。
