Sund Malin, Zeisberg Michael, Kalluri Raghu
Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02125, USA.
Gastroenterology. 2005 Dec;129(6):2076-91. doi: 10.1053/j.gastro.2005.06.023.
Progression of cancer is dependent on acquisition of vascular networks within the tumor. Tumor angiogenesis is dependent on up-regulation of angiogenesis stimulators to overcome the endogenous anti-angiogenic barrier. Such disruption of angiogenesis balance to favor neovascularization is a key step for progression of tumor growth and metastasis. In this regard, the vascular basement membrane and the extracellular matrix have been found to be rich sources of angiogenesis stimulators and inhibitors that become bioavailable on proteolysis of the matrix by tumor microenvironment-related enzymes. In this review the subgroup of endogenous angiogenesis stimulators and inhibitors is discussed, and their mechanism of action during tumor angiogenesis is evaluated. The role in regulating tumor growth and the possibility of using them as prognostic markers for human gastrointestinal cancers is discussed. Furthermore, we specifically address the role of vascular endothelial growth factor in human gastrointestinal cancers and discuss the development and use of bevacizumab (Avastin; anti-vascular endothelial growth factor antibody [Genentech, CA]) in the treatment of colorectal and other gastrointestinal cancers.
癌症的进展依赖于肿瘤内部血管网络的形成。肿瘤血管生成依赖于血管生成刺激因子的上调，以克服内源性抗血管生成屏障。这种血管生成平衡的破坏以利于新血管形成是肿瘤生长和转移进展的关键步骤。在这方面，已发现血管基底膜和细胞外基质是血管生成刺激因子和抑制剂的丰富来源，它们在肿瘤微环境相关酶对基质的蛋白水解作用下变得具有生物活性。在本综述中，讨论了内源性血管生成刺激因子和抑制剂的亚组，并评估了它们在肿瘤血管生成过程中的作用机制。还讨论了它们在调节肿瘤生长中的作用以及将其用作人类胃肠道癌症预后标志物的可能性。此外，我们特别探讨了血管内皮生长因子在人类胃肠道癌症中的作用，并讨论了贝伐单抗（阿瓦斯汀；抗血管内皮生长因子抗体[基因泰克公司，加利福尼亚州]）在治疗结直肠癌和其他胃肠道癌症中的研发和应用。
