p-glycoprotein expression in malignant melanoma.
In some human malignancies resistance to chemotherapy is caused by an energy-dependent efflux system, responsible for the removal of chemotherapeutics out of the resistant tumor cells. A major component of this efflux system is the permeability glycoprotein (p-glycoprotein), which depends on the multidrug-resistance gene MDR1. We have tested p-glycoprotein in primary and metastatic human melanoma by use of the monoclonal antibody C219; a substantial expression was only observed in 1/37 primary melanomas and in 1/27 melanoma metastases. None of the patients with negative metastases responded to chemotherapy. Moreover a complete remission of metastatic growth was observed in the patient with the metastasis significantly expressing the p-glycoprotein. Sequential studies revealed no significant increase of p-glycoprotein-positive cells during and after chemotherapy. We conclude that drug resistance in human melanoma does not usually depend on the p-glycoprotein-related efflux system. Other mechanisms are obviously responsible for drug resistance in this human malignancy.
Fuchs
B
B
Fachklinik Hornheide, Münster, Federal Republic of Germany.
Ostmeier
H
H
Suter
L
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004351:Drug Resistance / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins