Rooney P, Kumar S, Ponting J, Wang M
Christie Hospital, Manchester, UK.
Int J Cancer. 1995 Mar 3;60(5):632-6. doi: 10.1002/ijc.2910600511.
Tumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood-vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High-molecular-mass HA is anti-angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial-cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell-surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.
肿瘤的生长和转移完全依赖于新血管生成。肿瘤新血管生成的靶细胞是血管内皮细胞，肿瘤产生或诱导的特定血管生成分子被认为启动了这一过程。在本报告中，我们综述了其中一种血管生成分子——糖胺聚糖透明质酸（HA），它似乎因其分子量不同而在新血管生成中发挥不同作用。高分子量HA具有抗血管生成作用，而特定大小的HA寡糖则能积极刺激内皮细胞增殖和迁移，这是与新血管生成相关的两个关键事件，并能在体内诱导血管生成。我们详细介绍了HA寡糖对内皮细胞的作用，从与细胞表面受体结合，到激活信号转导途径、基因表达、蛋白质合成、细胞增殖和细胞迁移。我们还提出了一个模型，以解释在单个肿瘤的不同位置存在不同分子量的HA，以及这种HA如何促进肿瘤的整体生长和转移。
