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β1整合素在不同致瘤性的层粘连蛋白黏附选择的人结肠癌细胞系中的表达。

Expression of beta 1 integrin in laminin-adhesion-selected human colon cancer cell lines of varying tumorigenicity.

作者信息

Kim W H, Jun S H, Kibbey M C, Thompson E W, Kleinman H K

机构信息

Laboratory of Developmental Biology, National Institute of Dental Research, National Institute of Health, Bethesda, Md 20892, USA.

出版信息

Invasion Metastasis. 1994;14(1-6):147-55.

PMID:7544773
Abstract

Laminin has been shown to promote the malignant phenotype and the expression of certain laminin receptors has been correlated with the malignant character of the tumors. Here new cell lines were isolated from a human colon cancer cell line (LCC-C1) based on their adhesiveness to laminin. The laminin-adherent subclone formed large tumors in nude mice, whereas the laminin-nonadherent subclone failed to form sizable tumors. Only the laminin-adherent subclone adhered to laminin and invaded through Matrigel-coated filters. The adhesive and invasive ability of the cells was almost completely blocked by low concentrations (1.0 microgram/ml) of anti-beta 1 integrin antibody. The amounts of total cellular beta 1 integrin protein were similar in the two subclones when compared by Western blot, and the mRNA levels also did not differ. The localization of beta 1 integrin laminin receptor varied in the two subclones; the laminin-adherent subclone showed a linear distribution along the cell-cell junctions, while the laminin-nonadherent subclone did not stain between the cells. Using laminin-Sepharose affinity chromatography, more beta 1 integrin was obtained from the laminin-adherent subclone. These findings suggest that alterations in the affinity of beta 1 integrin for laminin and in its membrane distribution might be involved in the increased tumorigenicity observed in colon cancer cells.

摘要

层粘连蛋白已被证明可促进恶性表型,并且某些层粘连蛋白受体的表达与肿瘤的恶性特征相关。在此,基于它们对层粘连蛋白的粘附性,从人结肠癌细胞系(LCC-C1)中分离出新的细胞系。与层粘连蛋白粘附的亚克隆在裸鼠中形成大肿瘤,而与层粘连蛋白不粘附的亚克隆未能形成大小可观的肿瘤。只有与层粘连蛋白粘附的亚克隆能粘附于层粘连蛋白并穿过基质胶包被的滤膜侵袭。细胞的粘附和侵袭能力几乎完全被低浓度(1.0微克/毫升)的抗β1整合素抗体阻断。通过蛋白质印迹法比较,两个亚克隆中总的细胞β1整合素蛋白量相似,mRNA水平也无差异。β1整合素层粘连蛋白受体在两个亚克隆中的定位不同;与层粘连蛋白粘附的亚克隆在细胞间连接处呈线性分布,而与层粘连蛋白不粘附的亚克隆在细胞间无染色。使用层粘连蛋白-琼脂糖亲和层析,从与层粘连蛋白粘附的亚克隆中获得了更多的β1整合素。这些发现表明,β1整合素对层粘连蛋白的亲和力及其膜分布的改变可能与在结肠癌细胞中观察到的致瘤性增加有关。

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