神经节苷脂GD3与肿瘤的血管生成作用(英文)

Ganglioside GD3 and Tumor Angiogenesis

血管生成作用 (angiogenesis)是实体瘤 (solidtumor)生长和扩散的必要条件 .实体瘤的微血管密度与肿瘤的恶性程度成正相关 ,而且也与病人的预后密切相关 .因此 ,对抗血管生成作用是一种很有吸引力的肿瘤疗法 .神经节苷脂GD3在多种类型的肿瘤中超常表达 .一般认为 ,神经节苷脂GD3有增强肿瘤本身及邻近组织中的血管生成作用 ,从而促进肿瘤的演进和转移 .最近的研究工作为这一假设提供了有力的实验证据 .应用GD3合酶的反意DNA转染肿瘤细胞从而抑制细胞中的GD3合酶的表达 ,极大地降低了细胞的内源GD3含量 .进一步的研究证明 ,抑制肿瘤细胞的GD3合成明显地降低了该肿瘤细胞的血管内皮生长因子 (VEGF)的水平 ,并使血管生成作用降至最小限度 .这些实验说明GD3在肿瘤的血管生成中具有重要的作用 .此外 ,GD3作为肿瘤的一种相关抗原 。

Angiogenesis, the growth and formation of new blood vessels, is essential for the development and spread of solid tumors. Microvascular density is positively correlated with tumor malignancy and ultimately influences patient prognosis. Consequently, antiangiogenesis therapy is an attractive treatment for tumors. Ganglioside GD3 is over expressed in many types of tumors and is believed to stimulate tumor progression and metastasis by promoting angiogenesis in tumors and adjacent tissues. This has been demonstrated by recent studies in which tumor cells without ganglioside GD3 were engineered via an antisense strategy against GD3 synthase. Suppression of GD3 synthase expression in the engineered tumor cells results in minimal angiogenesis of the xenografts through down regulation of the angiogenic vascular epithelial growth factor (VEGF). This implicates an important role for GD3 in tumor angiogenesis. In addition to the biological function of GD3 in tumor growth, the synergic effects of tumor gangliosides and angiogenic factors on tumorigenicity should facilitate the use of combined gene therapy in the future.