Gollogly L, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
Neoplasma. 1996;43(5):285-9.
Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.
糖缀合物及其抗体是宿主与肿瘤相互作用的重要组成部分。本综述着重探讨关于α-半乳糖三联体研究的肿瘤学意义；α1→3半乳糖基表位（αGal）、负责其构建的酶α1,3半乳糖基转移酶（α1-3GT）及其相关抗体：抗α-半乳糖抗体。α-半乳糖表位以前被认为不存在于人体组织中，但已在几种人类癌细胞系、衰老红细胞和格雷夫斯病甲状腺细胞中得到证实。肿瘤细胞系上α-半乳糖的存在与动物模型中转移形成增加相关。人类对这些新抗原的反应机制很复杂，因为正常血清中天然抗α-半乳糖抗体的滴度很高，因此可以预测对表达α-半乳糖表位细胞的免疫识别。关于转移相关现象（如α-半乳糖的从头表达及其通过去唾液酸化而暴露）的致病作用，存在不同的假说。α-半乳糖在人体组织中偶尔表达的方式仍然未知，因为在组成性表达动物中产生这种表位的半乳糖基转移酶在人类基因组水平上发生了重大突变。病理上的重新表达被认为需要细胞水平上的许可性变化。详细了解这些改变是理解转移表型的先决条件。在这种背景下，还讨论了影响α-半乳糖表达的治疗策略的可能性。
