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Role of metallothionein in cisplatin sensitivity of germ-cell tumours

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Author: Meijer, C. · Timmer, A. · Vries, E.G.E.de · Groten, J.P. · Knol, A. · Zwart, N. · Dam, W.A. · Sleijfer, D.Th. · Mulder, N.H.
Type:article
Date:2000
Source:International Journal of Cancer, 6, 85, 777-781
Identifier: 235492
doi: doi:10.1002/(SICI)1097-0215(20000315)85:6<777::AID-IJC6>3.0.CO;2-D
Keywords: Nutrition · Cisplatin · Glutathione peroxidase · Metallothionein · Protein p53 · Article · Cellular distribution · Colon carcinoma · Disease association · Drug sensitivity · Germ cell tumor · Human · Human cell · Immunohistochemistry · Priority journal · Protein expression · Testis tumor · Antineoplastic Agents · Cisplatin · Colonic Neoplasms · Drug Screening Assays, Antitumor · Germinoma · Humans · Immunohistochemistry · Male · Metallothionein · Testicular Neoplasms · Tumor Cells, Cultured · Tumor Suppressor Protein p53 · Food and Nutrition · Healthy Living

Abstract

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. (C) 2000 Wiley-Liss, Inc.