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在具有不同转移潜能的人结肠癌亚系中,E-选择素依赖性黏附效率的差异

Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials.

作者信息

Sawada R, Tsuboi S, Fukuda M

机构信息

Glycobiology Program, La Jolla Cancer Research Foundation, California 92037.

出版信息

J Biol Chem. 1994 Jan 14;269(2):1425-31.

PMID:7507108
Abstract

Previously we have shown that high metastatic colonic carcinoma cells express relatively more lamp molecules and sialyl Le(x) structures on the cell surface than their corresponding low metastatic counterparts (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). In the present study, we extended these findings by testing whether these high and low metastatic colonic carcinoma cells differ in their adhesion efficiency to E-selectin-expressing cells. First, it was found that the high metastatic cells, as compared to their low metastatic counterparts, bind more efficiently to activated human endothelial cells that express E-selectin. This was also true when the adhesion was tested for Chinese hamster ovary cells stably expressing E-selectin. In addition, it was found that the high metastatic cells also adhere more efficiently to mouse endothelioma cells after activation with interleukin-1 beta. It was also shown that the adhesion can be inhibited by soluble lamp-1 or soluble leukosialin that contain sialy Le(x) termini. The inhibition was not, however, observed when these soluble glycoproteins lack sialyl Le(x) structures. The results indicate that the efficiency of the E-selectin-mediated binding of colonic carcinoma cells to human and mouse endothelial cells correlates with the metastatic potential of the cells and suggest that this adhesive event may be one of the critical factors for the metastatic spread of tumor cells. Soluble forms of leukosialin or lamp-1 may be useful as therapeutic agents for the inhibition of E-selectin-mediated binding to tumor cells.

摘要

先前我们已经表明,高转移性结肠癌细胞在细胞表面表达的溶酶体相关膜蛋白分子和唾液酸化路易斯寡糖(sialyl Le(x))结构比相应的低转移性细胞更多(斋藤,O.,王,W.-L.,洛坦,R.,福田,M.(1992年)《生物化学杂志》267卷,5700 - 5711页)。在本研究中,我们通过测试这些高转移性和低转移性结肠癌细胞对表达E - 选择素的细胞的黏附效率是否存在差异,扩展了这些发现。首先,发现与低转移性细胞相比,高转移性细胞更有效地结合到表达E - 选择素的活化人内皮细胞上。当对稳定表达E - 选择素的中国仓鼠卵巢细胞进行黏附测试时,情况也是如此。此外,还发现高转移性细胞在用白细胞介素 - 1β激活后,对小鼠内皮瘤细胞的黏附也更有效。还表明,黏附可被含有唾液酸化路易斯寡糖(sialy Le(x))末端的可溶性溶酶体相关膜蛋白1(lamp - 1)或可溶性白细胞涎酸蛋白抑制。然而,当这些可溶性糖蛋白缺乏唾液酸化路易斯寡糖(sialyl Le(x))结构时,未观察到抑制作用。结果表明,E - 选择素介导的结肠癌细胞与人和小鼠内皮细胞结合的效率与细胞的转移潜能相关,并表明这种黏附事件可能是肿瘤细胞转移扩散的关键因素之一。可溶性白细胞涎酸蛋白或溶酶体相关膜蛋白1(lamp - 1)形式可能作为抑制E - 选择素介导的与肿瘤细胞结合的治疗剂。

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