引用

为分析肿瘤转移机制，将小鼠Lewis肺癌亚链H7、C4反复注射C57BL/6小鼠，获得高转移亚链H7- a、H7- lu、H7- o、C4-sc、C4-ly。这些亚链在体外表现出增强的增殖和侵袭活性。神经节苷苷谱在高转移次细胞系中GM1表达低于亲本细胞系。在H7细胞中稳定沉默GM1合成酶，建立GM1- si -1和GM1- si -2。这些gm1敲除克隆的增殖和侵袭能力增强。然后，我们通过DNA芯片检测C4 vs. C4-ly或H7 vs. H7 (GM1-Si)组合中表达水平显著改变的基因。因此，在高转移亚系中，pp-GalNAc-T13基因被鉴定为上调基因。将pp-GalNAc-T13 cDNA稳定转染到C4 (T13-TF)中，可导致侵袭性和运动性增强。然后使用各种抗体和凝集素进行免疫印迹和流式细胞术。只有抗三聚体Tn抗体(mAb MLS128)在T13-TF克隆中表达量增加。 Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung metastasis than control clones. These data suggested that high expression of pp-GalNAc-T13 gene generated trimeric Tn antigen on Syndecan-1, leading to the enhanced metastasis.