Sawada T, Ho J J, Chung Y S, Sowa M, Kim Y S
Gastrointestinal Research Laboratory (151M2), Veterans Affairs Medical Center, San Francisco, CA 94121.
Int J Cancer. 1994 Jun 15;57(6):901-7. doi: 10.1002/ijc.2910570621.
Tumor cells interact with endothelial cells during both intra- and extravasation. Understanding how these interactions are modulated could lead to the development of ways to alter the metastatic potential of tumor cells. Three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-I, were examined for their ability to bind to the endothelial cell adhesion molecule E-selectin (ELAM-1). SW1990 cells exhibited highest binding, highest surface expression of the carbohydrate antigens sialylated Lewis(a) (sLe(a)) and sialylated Lewis(x) (sLe(x)) and released the most high m.w. sLe(a) and sLe(x) antigens. Expression of sLe(a) and sLe(x) antigens and binding to E-selectin were reduced by pre-treatment of SW1990 cells with the O-linked glycosylation inhibitor benzyl-alpha-GalNAc but not with the N-linked glycosylation inhibitor tunicamycin. Expression of peptide epitopes associated with MUC1 apomucins was increased by benzyl-alpha-GalNAc. Cell binding was greatly reduced by mucins purified from SW1990 xenografts and by an antibody against sLe(a). An antibody against sLe(x) had a much less marked effect. Sera from pancreatic cancer patients reduced SW1990 cell binding to E-selectin but sera from normals did not. The degree of inhibition was related to the sLe(x) level in the sample. When cancer serum was separated by column chromatography on Sephacryl S-400, the void volume fractions contained most of the sLe(a) and sLe(x) antigens and most of the inhibitory activity to E-selectin binding. Differences in the relative availability of sLe(a) and sLe(x) ligands on serum molecules and on the SW1990 cell surface may account for the differences between antibody and serum inhibition results. Thus SW1990 cell adhesion to E-selectin is mediated by ligands on mucinous glycoproteins, and adhesion can be inhibited by mucins, high blood levels of sLe(x) and reduction of cellular O-linked glycosylation.
肿瘤细胞在血管内渗和外渗过程中均与内皮细胞相互作用。了解这些相互作用是如何被调节的，可能会促使开发出改变肿瘤细胞转移潜能的方法。研究了三种胰腺癌细胞系SW1990、CAPAN - 2和PANC - 1与内皮细胞黏附分子E - 选择素（ELAM - 1）结合的能力。SW1990细胞表现出最高的结合能力、碳水化合物抗原唾液酸化刘易斯（a）（sLe（a））和唾液酸化刘易斯（x）（sLe（x））的最高表面表达，并释放出最高分子量的sLe（a）和sLe（x）抗原。用O - 连接糖基化抑制剂苄基 - α - N - 乙酰半乳糖胺预处理SW1990细胞后，sLe（a）和sLe（x）抗原的表达及与E - 选择素的结合减少，但用N - 连接糖基化抑制剂衣霉素预处理则无此现象。苄基 - α - N - 乙酰半乳糖胺可增加与MUC1脱辅基黏蛋白相关的肽表位的表达。从SW1990异种移植瘤中纯化的黏蛋白和抗sLe（a）抗体可大大降低细胞结合。抗sLe（x）抗体的作用则不太明显。胰腺癌患者的血清可降低SW1990细胞与E - 选择素的结合，但正常人的血清则无此作用。抑制程度与样本中的sLe（x）水平有关。当癌血清在Sephacryl S - 400上进行柱层析分离时，空体积级分含有大部分的sLe（a）和sLe（x）抗原以及大部分对E - 选择素结合的抑制活性。血清分子和SW1990细胞表面上sLe（a）和sLe（x）配体的相对可用性差异可能解释了抗体和血清抑制结果之间的差异。因此，SW1990细胞与E - 选择素的黏附是由黏液糖蛋白上的配体介导的，黏附可被黏蛋白、高血sLe（x）水平和细胞O - 连接糖基化的减少所抑制。
