E-selectin-dependent adhesion efficiency of colonic carcinoma cells is increased by genetic manipulation of their cell surface lysosomal membrane glycoprotein-1 expression levels.
E-selectin-dependent adhesion efficiency of colonic carcinoma cells is increased by genetic manipulation of their cell surface lysosomal membrane glycoprotein-1 expression levels.
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DOI：
10.1016/s0021-9258(18)31441-8
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发表时间：
1993-06
期刊：
影响因子：
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通讯作者：
R. Sawada;John;Lowe;Minoru FukudaT
中科院分区：
文献类型：
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作者：
R. Sawada;John;Lowe;Minoru FukudaT
溶酶体膜糖蛋白(lamp)-1和lamp-2是溶酶体膜内含量最多的糖蛋白。然而，少量的lamp-1和lamp-2分子可以存在于细胞表面。我们之前的研究表明，高转移性结肠癌L4细胞比低转移性SP细胞在细胞表面表达更多的lamp-1和lamp-2 （Saitoh， O., Wang, w . l .）。（1992）。化学，267,5700-5711)。由于lamp-1和lamp-2是能够显示唾液酰- le (x)末端的聚n -乙酰乳胺的主要载体，我们试图确定细胞表面增加的lamp-1数量是否会导致细胞表面唾液酰- le (x)决定因子的表达增加，并增加这些细胞对e -选择素的粘附。通过过表达lamp-1或在质膜上而不是溶酶体上优先表达突变的lamp-1分子，可以实现细胞表面lamp-1表达量的增加。表达不同量细胞表面lamp-1的细胞与活化的内皮细胞或表达e -选择素的中国仓鼠卵巢细胞的粘附性进行了测试。结果清楚地表明，与e -选择素和细胞表面唾液素- le (x)决定因子的粘附程度与细胞表面lamp-1的数量成正比。此外，研究表明，表达sialyl-Le(x)结构的中国仓鼠卵巢细胞产生的可溶性lamp-1可以抑制这种粘附。这些结果表明，lamp-1可以有效地为e -选择素提供配体，同时可以作为抑制e -选择素（也可能是p-选择素）介导的相互作用的有用试剂。
Lysosomal membrane glycoprotein (lamp)-1 and lamp-2 are the most abundant glycoproteins within the lysosomal membrane. A small amount of lamp-1 and lamp-2 molecules, however, can be present on the cell surface. We have shown previously that highly metastatic colonic carcinoma L4 cells express more lamp-1 and lamp-2 on the cell surface than low metastatic SP cells (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). Since lamp-1 and lamp-2 are the major carriers for poly-N-acetyllactosamines that are able to display sialyl-Le(x) termini, we sought to determine if an increased amount of lamp-1 on the cell surface would lead to increased expression of cell surface sialyl-Le(x) determinants and to the increased adhesion of those cells to E-selectin. Expression of increased amounts of lamp-1 on the cell surface was achieved either by overexpression of lamp-1 or by expressing a mutant lamp-1 molecule preferentially at the plasma membrane, rather than in lysosomes. Cells that express variable amounts of cell surface lamp-1 were tested for their adhesion to activated endothelial cells or E-selectin expressing Chinese hamster ovary cells. The results clearly show that the extent of adhesion to E-selectin and cell surface sialyl-Le(x) determinants is proportional to the amount of cell surface lamp-1. Moreover, it was demonstrated that such adhesion can be inhibited by soluble lamp-1 generated from Chinese hamster ovary cells expressing sialyl-Le(x) structures. These results indicate that lamp-1 can efficiently present ligands for E-selectin and at the same time can be a useful reagent for inhibition of E-selectin (and possibly P-selectin)-mediated interaction.