Role of gangliosides in tumour progression: A molecular target for cancer therapy?
Role of gangliosides in tumour progression: A molecular target for cancer therapy?
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DOI：
10.1016/s0306-9877(96)90014-6
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发表时间：
1996-02-01
影响因子：
4.7
通讯作者：
Fish, RG
中科院分区：
文献类型：
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作者：
Fish, RG
在许多患有神经外胚层或上皮来源的肿瘤的患者中，聚唾液酸化神经节苷脂（例如GD 3）过表达。神经节苷脂过度表达的机制可能是不同的两类肿瘤，并可能代表不同的继发性遗传突变或影响酶（转移酶和/或水解酶）控制这些神经节苷脂的代谢相互转化的表观遗传变化。已知神经外胚层来源的肿瘤细胞（例如，黑色素瘤和脑肿瘤）会产生和脱落聚唾液酸化神经节苷脂，而来自上皮来源的肿瘤细胞（例如，宫颈癌、肺癌、前列腺癌、乳腺癌、头颈癌、结肠癌和卵巢癌）的旁分泌信号可能会刺激肿瘤浸润间充质细胞（例如巨噬细胞和/或成纤维细胞）的过度表达和脱落。这种细胞膜过表达和酸性鞘糖脂脱落到癌症患者的间质空间和血液中可能在肿瘤细胞生长增加、免疫细胞识别缺乏和新血管形成中起核心作用，并且可能代表癌症治疗的分子靶点。
In a number of patients with tumours of either neuroectodermal or epithelial origin, polysialylated gangliosides (e.g. GD3) are over-expressed. The mechanism of ganglioside over-expression may be different for the two classes of tumour and could represent distinct secondary genetic mutations or epigenetic changes affecting the enzymes (transferases and/or hydrolases) controlling the metabolic interconversions of these gangliosides. Tumour cells of neuroectodermal origin (e.g, melanomas and brain tumours) are known to produce and shed polysialylated gangliosides, whereas paracrine signal(s) from tumour cells of epithelial origin (e.g. carcinomas of cervix, lung, prostate, breast, head and neck, colon and ovary) may stimulate over-expression and shedding from tumour infiltrating mesenchymal cells (e.g. macrophages and/or fibroblasts). This cellular membrane overexpression and shedding of acidic glycosphingolipids into the interstitial spaces and blood of cancer patients may play a central role in increased tumour cell growth, lack of immune cell recognition and neovascularization and could represent a molecular target for cancer therapy.