Differences in EGF related radiosensitisation of human squamous carcinoma cells with high and low numbers of EGF receptors.
Differences in EGF related radiosensitisation of human squamous carcinoma cells with high and low numbers of EGF receptors.
复制标题
DOI：
10.1038/bjc.1991.286
复制
发表时间：
1991-08
影响因子：
8.8
通讯作者：
Sutherland, R M
中科院分区：
文献类型：
--
作者：
Kwok, T T;Sutherland, R M
以前的研究表明，照射后表皮生长因子（EGF）的存在增强了CaSki细胞的放射敏感性。为了研究EGF受体密度和相关生长反应在EGF相关放射增敏中的作用，使用了四种人鳞状细胞癌细胞系。HN 5、A431、CaSki和SiHa细胞的EGF受体总数分别为5.2 × 10（6）、1.6 × 10（6）、7.9 × 10（5）和1.1 × 10（5），低亲和力EGF受体的解离常数（Kd）分别为11.8、3.8、1.7和0.8 nM。高亲和力受体的Kd在四种细胞系中略有不同，为0.09至0.21 nM。EGF对A431、CaSki和HN 5细胞的生长有抑制作用，但对SiHa细胞的生长有促进作用。由于存在10 ng ml-1的EGF照射后，放射敏感性增强相关的肩大小的生存曲线减少。A431、CaSki和HN 5细胞的致敏程度相似，对SiHa细胞没有影响。在此浓度下，EGF在照射后的克隆形成试验期间存在也降低了A431，CaSki和HN 5细胞的单层培养物的平板接种效率（PE），但增加了SiHa细胞的平板接种效率。小鼠3 T3细胞（少于5,000个受体）的辐射反应不受EGF的影响。在亲本和条件A431培养物中观察到EGF对辐射敏感性的类似水平的增强。条件细胞生长在50 ng ml-1的EGF为10周，并没有表现出生长抑制和PE减少与EGF治疗。这些细胞的EGF受体数量和结合亲和力与亲本细胞相同。条件细胞的结果支持EGF相关的放射增敏是EGF受体密度依赖性的假设。
Previous studies have shown that the presence of epidermal growth factor (EGF) after irradiation enhanced the radiosensitivity of CaSki cells. To examine the role of EGF receptor density and related growth response in EGF associated radiosensitisation, four human squamous carcinoma cell lines were used. The total number of EGF receptors for HN5, A431, CaSki, and SiHa cells is 5.2 x 10(6), 1.6 x 10(6), 7.9 x 10(5) and 1.1 x 10(5) respectively, and the dissociation constant (Kd) for low affinity EGF receptors is 11.8, 3.8, 1.7 and 0.8 nM respectively. The Kd for high affinity receptors differs slightly among the four cell lines, 0.09 to 0.21 nM. EGF inhibited the growth of A431, CaSki, and HN5 cells, but stimulated the growth of SiHa cells. Due to the presence of 10 ng ml-1 EGF after irradiation, radiosensitivity enhancement associated with reduced shoulder size of the survival curve was observed. The extent of sensitisation was similar for A431, CaSki, and HN5 cells, with no effect on SiHa cells. At this concentration, EGF present during the clonogenic assay period after irradiation also reduced the plating efficiency (PE) of the monolayer cultures of A431, CaSki, and HN5 cells, but increased that of SiHa cells. The radiation response of mouse 3T3 cells (less than 5,000 receptors) was not sensitised by EGF. A similar level of radiosensitivity enhancement by EGF was observed for parental and conditioned A431 cultures. The conditioned cells were grown in 50 ng ml-1 EGF for 10 weeks and did not demonstrate growth inhibition and PE reduction by treatment with EGF. The EGF receptor numbers and binding affinity of these cells were the same as for the parental cells. The results from the conditioned cells support the hypothesis that EGF related radiosensitisation is EGF receptor density dependent.