Fragoso Rita, Elias Ana Paula, Dias Sérgio
Angiogenesis Laboratory, CIPM/Instituto Portugues de Oncologia, Lisbon, Portugal.
Leuk Lymphoma. 2007 Mar;48(3):481-8. doi: 10.1080/10428190601064720.
Data obtained from animal models, and partially confirmed in pre-clinical studies, have provided clear evidence of the importance of angiogenesis for the growth of solid tumors. Similarly, in hematological cancers such as leukemias and lymphomas, the role of angiogenesis has been under intense scrutiny. However, the molecular singularities of leukemia, namely its cellular origin, have suggested a putative role for angiogenesis in these tumors may have distinct features. We and others have shown acute leukemia cells use angiogenic growth factor signaling pathways, namely those activated by vascular endothelial growth factor (VEGF) in autocrine and paracrine fashion. Autocrine and paracrine VEGF stimulation of subsets of leukemias results in cell proliferation, increased survival and migration. This review discusses recent advances in the field of leukemia angiogenesis, focusing on the role of VEGF and its receptors, acting in a paracrine or autocrine manner. We also briefly describe some of the novel anti-angiogenic compounds, namely VEGF blockers, and suggest their use to treat subsets of hematological malignancies may have clinical benefit.
从动物模型获得的数据，并在临床前研究中得到部分证实，已提供了明确证据，证明血管生成对实体瘤生长的重要性。同样，在白血病和淋巴瘤等血液系统癌症中，血管生成的作用也受到了密切关注。然而，白血病的分子独特性，即其细胞起源，表明血管生成在这些肿瘤中的假定作用可能具有不同特征。我们和其他人已经表明，急性白血病细胞利用血管生成生长因子信号通路，即那些由血管内皮生长因子（VEGF）以自分泌和旁分泌方式激活的信号通路。白血病亚群的自分泌和旁分泌VEGF刺激导致细胞增殖、存活率增加和迁移。本综述讨论了白血病血管生成领域的最新进展，重点关注以旁分泌或自分泌方式起作用的VEGF及其受体的作用。我们还简要描述了一些新型抗血管生成化合物，即VEGF阻滞剂，并表明它们用于治疗血液系统恶性肿瘤亚群可能具有临床益处。
