Meijer C, Timmer A, De Vries E G, Groten J P, Knol A, Zwart N, Dam W A, Sleijfer D T, Mulder N H
Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
Int J Cancer. 2000 Mar 15;85(6):777-81. doi: 10.1002/(sici)1097-0215(20000315)85:6<777::aid-ijc6>3.0.co;2-d.
Cisplatin (CDDP) is an extremely active drug in the treatment of germ-cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell-tumour and 3 colon-carcinoma cell lines. Major components of the sulfhydryl groups are glutathione and metallothionein (MT). We further investigated a possible role of MT in the CDDP sensitivity of germ-cell tumours. MT levels and functionality of the germ-cell-tumour and colon-carcinoma cell lines were found to be inversely correlated with CDDP sensitivity. No difference in sub-cellular localization of MT could be observed among the types of cell lines. In agreement with the in vitro data, immunohistochemical detection of MT was high in 11/14 primary human germ-cell tumours and low in 7/7 human colon carcinomas. MT-protein expression in primary germ-cell tumours did not discriminate between responding and non-responding patients. As compared with the primary tumours, MT-protein expression decreased in 5/7 post-chemotherapy residual vital tumours or remained undetectable (2/7). MT-protein expression in the germ-cell tumours was not related to total p53-protein expression. In summary, over-expression of MT was found in germ-cell tumours, both in cell lines and in human tumours. Although MT-protein over-expression seems to be associated with the CDDP sensitivity of germ-cell tumours, MT-protein expression in primary germ-cell tumours did not differ between responding and non-responding patients and therefore cannot be used to predict response to chemotherapy.
顺铂（CDDP）是治疗生殖细胞肿瘤的一种极具活性的药物。此前，我们在一组3种人类生殖细胞肿瘤和3种结肠癌细胞系中发现，巯基总量与CDDP敏感性之间存在意外的负相关。巯基的主要成分是谷胱甘肽和金属硫蛋白（MT）。我们进一步研究了MT在生殖细胞肿瘤CDDP敏感性中的可能作用。发现生殖细胞肿瘤和结肠癌细胞系的MT水平及功能与CDDP敏感性呈负相关。在不同类型的细胞系中，未观察到MT亚细胞定位的差异。与体外数据一致，免疫组化检测显示，11/14例原发性人类生殖细胞肿瘤中MT含量高，而7/7例人类结肠癌中MT含量低。原发性生殖细胞肿瘤中的MT蛋白表达在有反应和无反应的患者之间没有差异。与原发性肿瘤相比，5/7例化疗后残留的存活肿瘤中MT蛋白表达下降，或未检测到（2/7）。生殖细胞肿瘤中的MT蛋白表达与总p53蛋白表达无关。总之，在生殖细胞肿瘤的细胞系和人类肿瘤中均发现MT过表达。虽然MT蛋白过表达似乎与生殖细胞肿瘤的CDDP敏感性相关，但原发性生殖细胞肿瘤中的MT蛋白表达在有反应和无反应的患者之间没有差异，因此不能用于预测化疗反应。
