Role of metallothionein in cisplatin sensitivity of germ-cell tumours

Cisplatin (CDDP) is an extremely active drug in the treatment of germ-cell tumours. Earlier, we found an unexpected inverse correlation between the to tal 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 inve stigated 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 c ell lines were found to be inversely correlated with CDDP sensitivity. No d ifference in sub-cellular localization of MT could be observed among the ty pes 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 t umours 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 p5 3-protein expression. In summary, over-expression of MT was found in germ c ell tumours, both in cell lines and in human tumours. Although MT-protein o ver-expression seems to be associated with the CDDP sensitivity of germ-cel l tumours, MT-protein expression in primary germ-cell tumours did not diffe r between responding and non-responding patients and therefore cannot be us ed to predict response to chemotherapy. (C) 2000 Wiley-Liss, Inc.