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 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.
Meijer
C
C
Department of Medical Oncology, University Hospital, Groningen, The Netherlands. j.meijer@int.azg.nl
Timmer
A
A
De Vries
E G
EG
Groten
J P
JP
Knol
A
A
Zwart
N
N
Dam
W A
WA
Sleijfer
D T
DT
Mulder
N H
NH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D018237:Germinoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein; D002945:Cisplatin