Heymann D, Harb J, Ringeard S, Blanchard F, Lassort D, Raher S, Godard A
I.N.S.E.R.M. U211, Institute of Biology, Nantes, France.
J Cell Biochem. 1995 Jul;58(3):305-14. doi: 10.1002/jcb.240580305.
Integrins belong to a large family of heterodimeric membrane glycoproteins which mediate cell-cell or cell-extracellular matrix interactions. These interactions could play a major role during the migration of tumor cells across the extracellular matrix and vascular endothelium and would thus appear to be requisite for the metastatic process. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane alpha v beta 1 1.5-2-fold. The same phenomenon was observed on the SK-N-SH human neuroblastoma cell line. alpha v beta 1 upmodulation was concomitant with improved tumor cells attachment to the fibronectin matrix. This greater adhesion of tumor cells to fibronectin was inhibited by specific monoclonal antibodies against alpha v or beta 1 integrin subunits. Similar results were obtained after TNF-alpha treatment. Our findings demonstrate the ability of HILDA/LIF and OSM to modulate tumor cell capacity to adhere to the matrix component, suggesting a potential role for these cytokines in modulation of tumoral progression.
整合素属于一个由异二聚体膜糖蛋白组成的大家族,它介导细胞与细胞之间或细胞与细胞外基质之间的相互作用。这些相互作用在肿瘤细胞穿过细胞外基质和血管内皮的迁移过程中可能起主要作用,因此似乎是转移过程所必需的。用参与急性期反应的两种细胞因子HILDA/LIF或OSM对Foss人黑色素瘤细胞系进行预处理,可使膜αvβ1的表达增加1.5至2倍。在SK-N-SH人神经母细胞瘤细胞系上也观察到了同样的现象。αvβ1上调与肿瘤细胞对纤连蛋白基质的附着改善同时出现。肿瘤细胞对纤连蛋白的这种更强的黏附被针对αv或β1整合素亚基的特异性单克隆抗体所抑制。用肿瘤坏死因子-α处理后也得到了类似的结果。我们的研究结果表明,HILDA/LIF和OSM有能力调节肿瘤细胞黏附于基质成分的能力,提示这些细胞因子在调节肿瘤进展中可能发挥潜在作用。