Neskey David M, Ambesi Anthony, Pumiglia Kevin M, McKeown-Longo Paula J
Center for Cell Biology & Cancer Research, Albany Medical College, Albany, New York 12208, USA.
J Exp Clin Cancer Res. 2008 Nov 4;27(1):61. doi: 10.1186/1756-9966-27-61.
Endostatin and anastellin, fragments of collagen type XVIII and fibronectin, respectively, belong to a family of endogenous inhibitors of angiogenesis which inhibit tumor growth and metastasis in a number of mouse models of human cancer. The mechanism of action of these inhibitors is not well understood, but they have great potential usefulness as non-toxic long-term therapy for cancer treatment.
In this study, we compare the anti-angiogenic properties of endostatin and anastellin using cell proliferation and transwell migration assays.
Anastellin but not endostatin completely inhibited human dermal microvessel endothelial cell proliferation in response to serum stimulation. Both anastellin and endostatin additively inhibited endothelial cell migration in response to VEGF. Anastellin but not endostatin lowered basal levels of active ERK.
These data indicate that anastellin and endostatin exert their anti-angiogenic effects by modulating distinct steps in the angiogenic pathway and suggest that matrix-derived inhibitors of angiogenesis may exhibit higher efficacy when used in combination.
内皮抑素和血管抑素分别是ⅩⅧ型胶原蛋白和纤连蛋白的片段，属于内源性血管生成抑制剂家族，在多种人类癌症小鼠模型中可抑制肿瘤生长和转移。这些抑制剂的作用机制尚不完全清楚，但作为癌症治疗的无毒长期疗法，它们具有很大的潜在应用价值。
在本研究中，我们使用细胞增殖和Transwell迁移试验比较了内皮抑素和血管抑素的抗血管生成特性。
血管抑素而非内皮抑素能完全抑制血清刺激下人真皮微血管内皮细胞的增殖。内皮抑素和血管抑素均能协同抑制血管内皮生长因子（VEGF）诱导的内皮细胞迁移。血管抑素而非内皮抑素降低了活性细胞外信号调节激酶（ERK）的基础水平。
这些数据表明，血管抑素和内皮抑素通过调节血管生成途径中的不同步骤发挥其抗血管生成作用，并提示基质衍生的血管生成抑制剂联合使用时可能具有更高的疗效。
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