Boligan Kayluz Frias, Mesa Circe, Fernandez Luis Enrique, von Gunten Stephan
Institute of Pharmacology, University of Bern, Friedbühlstrasse 49, 3010, Bern, Switzerland,
Cell Mol Life Sci. 2015 Apr;72(7):1231-48. doi: 10.1007/s00018-014-1799-5. Epub 2014 Dec 7.
Aberrant glycosylation is a key feature of malignant transformation and reflects epigenetic and genetic anomalies among the multitude of molecules involved in glycan biosynthesis. Although glycan biosynthesis is not template bound, altered tumor glycosylation is not random, but associated with common glycosylation patterns. Evidence suggests that acquisition of distinct glycosylation patterns evolves from a 'microevolutionary' process conferring advantages in terms of tumor growth, tumor dissemination, and immune escape. Such glycosylation modifications also involve xeno- and hypersialylation. Xeno-autoantigens such as Neu5Gc-gangliosides provide potential targets for immunotherapy. Hypersialylation may display 'enhanced self' to escape immunosurveillance and involves several not mutually exclusive inhibitory pathways that all rely on protein-glycan interactions. A better understanding of tumor 'glycan codes' as deciphered by lectins, such as siglecs, selectins, C-type lectins and galectins, may lead to novel treatment strategies, not only in cancer, but also in autoimmune disease or transplantation.
异常糖基化是恶性转化的一个关键特征，反映了参与聚糖生物合成的众多分子中的表观遗传和基因异常。尽管聚糖生物合成不受模板限制，但肿瘤糖基化的改变并非随机发生，而是与常见的糖基化模式相关。有证据表明，独特糖基化模式的获得源于一个“微进化”过程，该过程在肿瘤生长、肿瘤播散和免疫逃逸方面赋予优势。这种糖基化修饰还涉及异种糖基化和高唾液酸化。诸如Neu5Gc-神经节苷脂等异种自身抗原为免疫治疗提供了潜在靶点。高唾液酸化可能表现出“增强的自身”以逃避免疫监视，并且涉及几个并非相互排斥的抑制途径，所有这些途径都依赖于蛋白质-聚糖相互作用。更好地理解由凝集素（如唾液酸结合免疫球蛋白样凝集素、选择素、C型凝集素和半乳糖凝集素）解读的肿瘤“聚糖密码”，可能会带来新的治疗策略，不仅适用于癌症，也适用于自身免疫性疾病或移植。
