Liu N, Lapcevich R K, Underhill C B, Han Z, Gao F, Swartz G, Plum S M, Zhang L, Green S J
Department of Oncology, Georgetown University Medical Center, Washington, DC 20007 USA.
Cancer Res. 2001 Feb 1;61(3):1022-8.
In this study, a hyaluronan-binding complex, which we termed Metastatin, was isolated from bovine cartilage by affinity chromatography and found to have both antitumorigenic and antiangiogenic properties. Metastatin was able to block the formation of tumor nodules in the lungs of mice inoculated with B16BL6 melanoma or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into chicken embryos inhibited the growth of both B16BL6 mouse melanoma and TSU human prostate cancer cells growing on the chorioallantoic membrane. The in vivo biological effect may be attributed to the antiangiogenic activity because Metastatin is able to inhibit the migration and proliferation of cultured endothelial cells as well as vascular endothelial growth factor-induced angiogenesis on the chorioallantoic membrane. In each case, the effect could be blocked by either heat denaturing the Metastatin or premixing it with hyaluronan, suggesting that its activity critically depends on its ability to bind hyaluronan on the target cells. Collectively, these results suggest that Metastatin is an effective antitumor agent that exhibits antiangiogenic activity.
在本研究中，一种我们称为“Metastatin”的透明质酸结合复合物通过亲和层析从牛软骨中分离出来，发现其具有抗肿瘤和抗血管生成特性。Metastatin能够阻止接种B16BL6黑色素瘤或Lewis肺癌细胞的小鼠肺部肿瘤结节的形成。将Metastatin单次静脉注射到鸡胚中，可抑制在尿囊绒毛膜上生长的B16BL6小鼠黑色素瘤细胞和TSU人前列腺癌细胞的生长。体内生物学效应可能归因于抗血管生成活性，因为Metastatin能够抑制培养的内皮细胞的迁移和增殖以及尿囊绒毛膜上血管内皮生长因子诱导的血管生成。在每种情况下，通过对Metastatin进行热变性或使其与透明质酸预混合，均可阻断其作用，这表明其活性关键取决于其与靶细胞上透明质酸结合的能力。总体而言，这些结果表明Metastatin是一种具有抗血管生成活性的有效抗肿瘤药物。
