Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Semin Thromb Hemost. 2010 Apr;36(3):321-31. doi: 10.1055/s-0030-1253454. Epub 2010 May 20.
The blood vessels supplying tumors are strikingly heterogeneous and differ from their normal counterparts with respect to organization, structure, and function. Six distinctly different tumor vessel types have been identified, and much has been learned about the steps and mechanisms by which they form. Four of the six vessel types (mother vessels, capillaries, glomeruloid microvascular proliferations, and vascular malformations) develop from preexisting normal venules and capillaries by angiogenesis. The two remaining vessel types (feeder arteries and draining veins) develop from arterio-venogenesis, a parallel, poorly understood process that involves the remodeling of preexisting arteries and veins. All six of these tumor vessel types can be induced to form sequentially in normal mouse tissues by an adenoviral vector expressing vascular endothelial growth factor (VEGF)-A164. Current antiangiogenic cancer therapies directed at VEGF-A or its receptors have been of only limited benefit to cancer patients, perhaps because they target only the endothelial cells of the tumor blood vessel subset that requires exogenous VEGF-A for maintenance. A goal of future work is to identify therapeutic targets on tumor blood vessel endothelial cells that have lost this requirement.
供应肿瘤的血管非常不均匀，在组织、结构和功能上与正常血管不同。已经确定了六种截然不同的肿瘤血管类型，并且已经了解了它们形成的步骤和机制。这六种血管类型中的四种（母血管、毛细血管、肾小球样微血管增生和血管畸形）是通过血管生成从预先存在的正常小静脉和毛细血管发育而来的。其余两种血管类型（供血动脉和引流静脉）是由动静脉生成发育而来的，这是一个平行的、尚未被充分理解的过程，涉及到预先存在的动脉和静脉的重塑。通过表达血管内皮生长因子（VEGF）-A164 的腺病毒载体，可以在正常小鼠组织中依次诱导形成这六种肿瘤血管类型。目前针对 VEGF-A 或其受体的抗血管生成癌症治疗对癌症患者的疗效有限，这可能是因为它们只针对肿瘤血管亚组的内皮细胞起作用，而这些内皮细胞需要外源性 VEGF-A 来维持。未来工作的目标是确定肿瘤血管内皮细胞上失去这种需求的治疗靶点。
