Birklé S, Zeng G, Gao L, Yu R K, Aubry J
Ecole Nationale Vétérinaire, Nantes, France.
Biochimie. 2003 Mar-Apr;85(3-4):455-63. doi: 10.1016/s0300-9084(03)00006-3.
Neuroectodermic tumors can mostly be characterized by the presence of tumor-associated glycosphingolipid antigens, such as gangliosides, defined by monoclonal antibodies. Recently, cumulative evidence indicates that gangliosides modify the biological effects of several trophic factors, in vitro and in vivo, as well as the mitogenic signaling cascade that these factors generate. The functional roles of gangliosides in tumor progression can be revisited: (i) ganglioside antigens on the cell surface, or shed from the cells, act as immunosuppressors, as typically observed for the suppression of cytotoxic T cells and dendritic cells, (ii) certain gangliosides, such as GD3 or GM2, promote tumor-associated angiogenesis, (iii) gangliosides strongly regulate cell adhesion/motility and thus initiate tumor metastasis, (iv) ganglioside antigens are directly connected with transducer molecules in microdomains to initiate adhesion coupled with signaling, and (v) ganglioside antigens and their catabolites are modulators of signal transduction through interaction with tyrosine kinases associated with growth factor receptors or other protein kinases. Given the potential importance of these sialylated gangliosides and their modulating biological behavior in vivo, further studies on the role of gangliosides are warranted.
神经外胚层肿瘤大多可通过存在肿瘤相关糖鞘脂抗原（如神经节苷脂）来表征，这些抗原由单克隆抗体定义。最近，越来越多的证据表明，神经节苷脂在体外和体内会改变几种营养因子的生物学效应，以及这些因子产生的有丝分裂信号级联反应。神经节苷脂在肿瘤进展中的功能作用可以重新审视：（i）细胞表面或从细胞脱落的神经节苷脂抗原作为免疫抑制剂，如通常观察到的对细胞毒性T细胞和树突状细胞的抑制作用；（ii）某些神经节苷脂，如GD3或GM2，促进肿瘤相关的血管生成；（iii）神经节苷脂强烈调节细胞黏附/运动，从而引发肿瘤转移；（iv）神经节苷脂抗原在微结构域中与转导分子直接相连，以启动与信号传导相关的黏附；（v）神经节苷脂抗原及其分解代谢产物通过与生长因子受体相关的酪氨酸激酶或其他蛋白激酶相互作用，成为信号转导的调节剂。鉴于这些唾液酸化神经节苷脂及其在体内调节生物学行为的潜在重要性，有必要对神经节苷脂的作用进行进一步研究。
