Meineke Viktor, Gilbertz Klaus-Peter, Schilperoort Karen, Cordes Nils, Sendler Andreas, Moede Tilo, van Beuningen Dirk
Institute of Radiobiology, Federal Armed Forces, Munich, Germany.
Strahlenther Onkol. 2002 Dec;178(12):709-14. doi: 10.1007/s00066-002-0993-9.
Adhesion of tumor cells to endothelial cells and to the extracellular matrix is a key step in the initial phase of metastasis. Since radiotherapy of tumors can induce alterations of the cell surface, we investigated the effect of ionizing radiation on the expression of integrins in the colorectal tumor cell line COLO-320 and the modulation of adhesion capacity of irradiated cells to collagen and fibronectin.
The cell surface expression of a broad range of integrins on COLO-320 cells was determined by flow cytometry during 144 hours after X-irradiation. The functional significance of increased adhesion molecule expression was assessed by cell-matrix adhesion and receptor blocking experiments.
Cell surface expression of the following integrin alpha and beta subunits was quantified: beta1 (CD29), alpha 2 (CD49b), alpha 5 (CD49e) and alpha 6 (CD49f). The expression of alpha 1, alpha 2, alpha 5, and alpha 6 changes as a function of time after irradiation (5 Gy). For beta1 even a function of dose (1-5 Gy) could be shown. Adhesion experiments confirmed a time dependent increase in adhesion to both collagen and fibronectin. Radiation-induced increase in adhesion was inhibited significantly by using a CD29 antibody.
Ionizing radiation modulates cell surface expression of integrins and cell-matrix interactions. The beta1-integrin subunit plays an important role in radiation-induced adhesion to both collagen and fibronectin. Possible consequences of these in-vitro results for radiotherapy of colorectal tumors in vivo are discussed.
肿瘤细胞与内皮细胞以及细胞外基质的黏附是转移初始阶段的关键步骤。由于肿瘤放疗可诱导细胞表面发生改变,我们研究了电离辐射对大肠肿瘤细胞系COLO - 320中整合素表达的影响,以及辐射后细胞对胶原蛋白和纤连蛋白黏附能力的调节。
通过流式细胞术测定X射线照射后144小时内COLO - 320细胞上多种整合素的细胞表面表达。通过细胞 - 基质黏附实验和受体阻断实验评估黏附分子表达增加的功能意义。
对以下整合素α和β亚基的细胞表面表达进行了定量:β1(CD29)、α2(CD49b)、α5(CD49e)和α6(CD49f)。照射(5 Gy)后,α1、α2、α5和α6的表达随时间变化。对于β1,甚至显示出剂量(1 - 5 Gy)依赖性。黏附实验证实,细胞对胶原蛋白和纤连蛋白的黏附随时间增加。使用CD29抗体可显著抑制辐射诱导的黏附增加。
电离辐射调节整合素的细胞表面表达和细胞 - 基质相互作用。β1整合素亚基在辐射诱导的细胞对胶原蛋白和纤连蛋白的黏附中起重要作用。讨论了这些体外结果对体内大肠肿瘤放疗的可能影响。