GLUTATHIONE AND RELATED ENZYMES IN TUMOR PROGRESSION AND METASTASES OF HUMAN-MELANOMA

被引:43
作者
SCHADENDORF, D
JURGOVSKY, K
KOHLMUS, CM
CZARNETSKI, BM
机构
[1] University Hospital Rudolf Virchow, HU Berlin, Department of Dermatology, 13353 Berlin
关键词
GLUTATHIONE-S-TRANSFERASE; GAMMA-GLUTAMYL-TRANSPEPTIDASE; GLUTATHIONE REDUCTASE; DRUG RESISTANCE;
D O I
10.1111/1523-1747.ep12313403
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
We have shown previously that overexpression of p-170 glycoprotein-mediated multidrug resistance plays only a minor role in conferring chemoresistance to human melanoma cells, In addition to membrane transporters like p-170, metabolizing enzyme systems have been implicated in altered drug sensitivity, Recently, glutathione and associated enzymes have been associated with resistance to alkylating substances, particularly in gastrointestinal and gynecologic cancers, In this study, we investigated whether increased levels of glutathione and related enzymes map play a role in chemoresistance in melanoma, Levels of glutathione, glutathione S-transferase (GST), glutathione reductase, and gamma-glutamyl transpeptidase were analyzed in melanoma and nonmelanoma cell lines, In addition, 18 melanoma metastases derived from skin and lymph nodes were examined, Levels of gamma-glutamyl transpeptidase were statistically different in cells derived from melanocytic tumors compared with non-melanoma cell lines and normal cells, In addition, GST levels in metastases derived from skin or lymph nodes were significantly lower than those in permanent cell lines, However, levels of glutathione and related enzymes in metastases and cell lines fluctuated over a wide range, up to 40-fold, regardless of treatment status or origin of metastases, In a second part of the study, the expression of GST isoenzymes alpha, mu, and pi, was studied by immunohistology in 10 benign nevi, 29 primary melanomas, and 39 melanoma metastases before and during chemotherapy. Expression of GST isoenzymes was increased with tumor progression, and GST rr was the strongest isoform expressed, However, no correlation was found between GST levels by immunohistochemistry and the course of tumor progression, between GST levels in metastases obtained before or during chemotherapy, or between GST levels and clinical response, These data suggest that alterations in glutathione metabolism and the expression of GST do not play a major role in resistance to chemotherapeutic drugs in melanoma.
引用
收藏
页码:109 / 112
页数:4
相关论文
共 38 条
[1]   RELATIONSHIP BETWEEN MELANOGENESIS, GLUTATHIONE LEVELS AND MELPHALAN TOXICITY IN HUMAN-MELANOMA CELLS [J].
BENATHAN, M ;
ALVEROJACKSON, H ;
MOOY, AM ;
SCALETTA, C ;
FRENK, E .
MELANOMA RESEARCH, 1992, 2 (5-6) :305-314
[2]  
BLACK SM, 1989, BIOCHEM J, V268, P309
[3]   DO GLUTATHIONE AND RELATED ENZYMES PLAY A ROLE IN DRUG-RESISTANCE IN SMALL-CELL LUNG-CANCER CELL-LINES [J].
CAMPLING, BG ;
BAER, K ;
BAKER, HM ;
LAM, YM ;
COLE, SPC .
BRITISH JOURNAL OF CANCER, 1993, 68 (02) :327-335
[4]  
CARLBERG I, 1975, J BIOL CHEM, V250, P5475
[5]  
CHARKRABORTY AK, 1992, MELANOMA RES, V2, P315
[6]   GLUTATHIONE-S-TRANSFERASE EXPRESSION IN BENIGN AND MALIGNANT OVARIAN-TUMORS [J].
GREEN, JA ;
ROBERTSON, LJ ;
CLARK, AH .
BRITISH JOURNAL OF CANCER, 1993, 68 (02) :235-239
[7]  
HABIG WH, 1974, J BIOL CHEM, V249, P7130
[8]  
HANADA K, 1991, Journal of Dermatological Science, V2, P18, DOI 10.1016/0923-1811(91)90038-Y
[9]   MECHANISMS OF MULTIDRUG RESISTANCE IN CANCER-TREATMENT [J].
HARRIS, AL ;
HOCHHAUSER, D .
ACTA ONCOLOGICA, 1992, 31 (02) :205-213
[10]   THERAPY FOR CUTANEOUS MELANOMA - AN UPDATE [J].
HO, VC ;
SOBER, AJ .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1990, 22 (02) :159-176