Ardini E, Tagliabue E, Magnifico A, Butò S, Castronovo V, Colnaghi M I, Ménard S
Division of Experimental Oncology E, Istituto Nazionale Tumori, 20133 Milan, Italy.
J Biol Chem. 1997 Jan 24;272(4):2342-5. doi: 10.1074/jbc.272.4.2342.
The interactions between tumor cells and laminin or other components of the extracellular matrix have been shown to play an important role in tumor invasion and metastasis. However, the role of the monomeric 67-kDa laminin receptor (67LR) remains unclear. We analyzed the regulation of 67LR expression under different culture conditions with respect to the expression of other well characterized laminin receptors. In A431 cells treated with laminin for different time periods, the regulation of 67LR expression correlated with expression of the alpha6 integrin subunit but not with the expression of other laminin receptors. Moreover, cytokine treatment resulted in down-modulated expression of the alpha6 integrin subunit and the 67LR. Co-regulation of the expression of the two receptors was further suggested by the observation that specific down-modulation of the alpha6-chain by antisense oligonucleotides was accompanied by a proportional decrease in the cell surface expression of 67LR. Biochemical analyses indicated co-immunoprecipitation of 67LR and the alpha6 subunit with an anti-alpha6 but not an anti-beta1 monoclonal antibody. Co-regulation of 67LR and alpha6 subunit expression, together with the physical association between the two receptors, supports the hypothesis that 67LR is an auxiliary molecule involved in regulating or stabilizing the interaction of laminin with the alpha6beta4 integrin.
肿瘤细胞与层粘连蛋白或细胞外基质的其他成分之间的相互作用已被证明在肿瘤侵袭和转移中起重要作用。然而，单体67-kDa层粘连蛋白受体（67LR）的作用仍不清楚。我们分析了在不同培养条件下67LR表达的调控情况，并与其他已明确特征的层粘连蛋白受体的表达进行了比较。在用层粘连蛋白处理不同时间段的A431细胞中，67LR表达的调控与α6整合素亚基的表达相关，而与其他层粘连蛋白受体的表达无关。此外，细胞因子处理导致α6整合素亚基和67LR的表达下调。通过反义寡核苷酸特异性下调α6链伴随着67LR细胞表面表达成比例下降这一观察结果，进一步提示了这两种受体表达的共同调控。生化分析表明，用抗α6单克隆抗体而非抗β1单克隆抗体可共免疫沉淀67LR和α6亚基。67LR和α6亚基表达的共同调控，以及这两种受体之间的物理关联，支持了67LR是参与调节或稳定层粘连蛋白与α6β4整合素相互作用的辅助分子这一假说。
