Nouri A M, Hussain R F, Oliver R T
Department of Medical Oncology, Royal London Hospital, Whitechapel, U.K.
Eur J Cancer. 1995 Jun;31A(6):963-9. doi: 10.1016/0959-8049(95)00120-4.
Using radiobinding, transfection and colorimetric assays, the biological significance of epidermal growth factor (EGF) and its receptor on established human tumour cell lines was investigated. The intensity of class I major histocompatibility antigen (MHC) and EGF receptor (EGFR) expression on 20 tumour cell lines was investigated and showed no direct correlation (coefficient of correlation r = 0.43 and P = 0.06). furthermore, transfection of the beta 2-microglobulin gene into a class I negative bladder tumour cell line, resulting in the re-expression of fully assembled cell surface class I antigens, did not result in alteration of EGFR expression. However, there was an inverse correlation between the intensity of EGFR expression and the stimulatory response of cells to exogenously added EGF. The per cent inhibitions of cell proliferation by EGF at 100 ng/ml for A431 (highest EGFR expressor) and Scaber (lowest EGFR expressor) were 37 and -7%, respectively. The results also showed that cell lines isolated from testis tumours positive for epithelial markers (using pan keratin antibody LP34 as an epithelial marker), expressed significantly lower EGFR levels than cell lines from bladder tumours. The expression of EGFR receptor was not modulated by interferons (IFN-alpha and -gamma and only a minor effect with IFN-beta) or active supernatant containing a mixture of cytokines. Whilst the pretreatment of tumour cells with IFNs resulted in a significant increase in the susceptibility of tumour cells to interleukin-2-activated peripheral blood mononuclear cells, EGF treatment resulted in their protection. Thus, the per cent killing at an effector:target ratio of 20:1 for untreated cells and EGF (100 ng/ml), IFN-alpha (1000 U/ml), -beta (2000 U/ml) and -gamma (100 U/ml) were 53%, 33% (P = 0.004), 64% (P = 0.004), 69% (P = 0.001) and 66% (P = 0.001), respectively. These results indicate the complex interactions between EGF and EGFR and their relevance in modifying tumour cell behaviour. The hypothesis that the resistance to cytolysis of tumour cells induced by EGF stimulation may be a factor in the accelerated tumour growth seen in patients after traumatic tissue damage is discussed.
利用放射结合、转染和比色分析，研究了表皮生长因子（EGF）及其受体对已建立的人肿瘤细胞系的生物学意义。研究了20种肿瘤细胞系上I类主要组织相容性抗原（MHC）和EGF受体（EGFR）的表达强度，结果显示二者无直接相关性（相关系数r = 0.43，P = 0.06）。此外，将β2-微球蛋白基因转染至I类阴性膀胱肿瘤细胞系，导致细胞表面完全组装的I类抗原重新表达，但并未改变EGFR的表达。然而，EGFR表达强度与细胞对外源性添加EGF的刺激反应呈负相关。100 ng/ml的EGF对A431（EGFR表达最高者）和Scaber（EGFR表达最低者）细胞增殖的抑制百分比分别为37%和 -7%。结果还表明，从睾丸肿瘤中分离出的上皮标志物呈阳性的细胞系（使用泛角蛋白抗体LP34作为上皮标志物），其EGFR水平明显低于膀胱肿瘤细胞系。EGFR受体的表达不受干扰素（IFN-α、-γ，IFN-β仅有轻微影响）或含有细胞因子混合物的活性上清液的调节。虽然用干扰素预处理肿瘤细胞会导致肿瘤细胞对白细胞介素-2激活的外周血单核细胞的敏感性显著增加，但EGF处理则会使其受到保护。因此，效应细胞与靶细胞比例为20:1时，未处理细胞以及EGF（100 ng/ml）、IFN-α（1000 U/ml）、-β（2000 U/ml）和 -γ（100 U/ml）处理后的细胞杀伤百分比分别为53%、33%（P = 0.004）、64%（P = 0.004）、69%（P = 0.001）和66%（P = 0.001）。这些结果表明EGF和EGFR之间存在复杂的相互作用，以及它们在改变肿瘤细胞行为方面的相关性。文中还讨论了EGF刺激诱导的肿瘤细胞对细胞溶解的抗性可能是创伤组织损伤后患者肿瘤加速生长的一个因素这一假说。
