低转移性和高转移性人结肠癌异种移植物中α 6、β 1和β 4整合素亚基的表达、基底膜组织和蛋白水解能力

Invasion & metastasis Pub Date : 1995-01-01
N Daémi, T Vallet, N Thomasset, M F Jacquier, N Zebda, J F Doré, B Sordat, L Rémy
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引用次数: 0

摘要

恶性转化与细胞-细胞和细胞-基质相互作用的改变有关。E2和C5克隆来源于人结肠腺癌LoVo细胞系,分别表现出低和高的体内转移能力。在这项研究中,我们评估了E2和C5细胞在基膜层粘连蛋白上的粘附和扩散,层粘连蛋白受体整合素α 6 β 1和α 6 β 4的表达以及明胶溶解和纤溶酶原依赖活性的表达。在免疫抑制的新生大鼠皮下移植后的第5天和第7天,分化良好的E2肿瘤显示出这些整合素亚基的极化表达,但β 1亚基保留在细胞周围。相比之下,C5肿瘤是无组织的,三个整合素亚单位仍然是非极化和细胞周围。流式细胞术结果显示,高转移性C5克隆中α 6 β 1和α 1 β 4整合素的表达弱于E2克隆,而层粘连蛋白的表达无显著差异。与E2细胞相比,C5细胞中这些整合素受体的低表达和细胞周围定位可能解释了它们在层粘连蛋白上的结合和扩散能力、肿瘤周围基底膜的组织和分化表型的维持方面的差异。虽然在两个克隆的培养上清中检测到类似水平的明胶溶酶和纤溶酶原激活剂活性,但组织酶谱图显示,在C5和亲代肿瘤切片中,纤溶酶原依赖性酪蛋白溶解比E2异种移植物更早出现。这些结果表明,体内C5肿瘤的侵袭性增强可能与整合素表达不足和分布导致基底膜设置受损以及肿瘤/宿主相互作用调节的蛋白水解活性有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expression of the alpha 6, beta 1 and beta 4 integrin subunits, basement membrane organization and proteolytic capacities in low and high metastatic human colon carcinoma xenografts.

Malignant transformation is associated with alterations in both cell-cell and cell-matrix interactions. The E2 and C5 clones, derived from the human colon adenocarcinoma LoVo cell line, show, respectively, low and high metastatic capacity as experimental xenografts in vivo. In this study, we have assessed the adhesion and spreading of E2 and C5 cells on basement membrane laminin, expression of the laminin receptor integrins alpha 6 beta 1 and alpha 6 beta 4 and expression of gelatinolytic and plasminogen-dependent activities. On days 5 and 7 after subcutaneous grafting to immunosuppressed newborn rats, well-differentiated E2 tumors displayed a polarized expression of these integrin subunits, with the exception of the beta 1 subunit which remained pericellular. In contrast, C5 tumors were unorganized and the three integrin subunits remained nonpolarized and pericellular. Flow cytometry results showed that the expression of alpha 6 beta 1 and alpha 1 beta 4 integrins was weaker in the highly metastatic C5 clone than in the E2 clone whereas laminin expression was not significantly different. Under-expression and pericellular localization of these integrin receptors in C5 cells as compared to E2 cells may explain the difference in their binding and spreading capacity on laminin, organization of peritumoral basement membrane and maintenance of a differentiated phenotype. Whereas similar levels of gelatinolytic and plasminogen activator activities have been detected in the culture supernatant of the two clones, histozymograms showed that plasminogen-dependent caseinolysis appeared earlier in sections of C5 and parental tumors than in those of E2 xenografts. These results suggest that enhanced aggressiveness of C5 tumors in vivo may be linked to both an impairment of basement membrane setting due to integrin underexpression and distribution and of proteolytic activities modulated by tumor/host interactions.

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