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p-glycoprotein expression in malignant melanoma
1Fachklinik Hornheide, Münster, Federal Republic of Germany.
Abstract:
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.
Insights
Drug resistance in human melanoma is typically not due to p-glycoprotein efflux. This study found limited p-glycoprotein expression in melanoma, suggesting other mechanisms drive chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chemotherapy resistance in human malignancies can stem from energy-dependent efflux systems.
- The permeability glycoprotein (p-glycoprotein), encoded by the multidrug-resistance gene MDR1, is a key component of these efflux systems.
Purpose of the Study:
- To investigate the role of p-glycoprotein expression in primary and metastatic human melanoma.
- To determine if p-glycoprotein expression correlates with chemotherapy response in melanoma patients.
Main Methods:
- Utilized the monoclonal antibody C219 to assess p-glycoprotein expression in melanoma samples.
- Correlated p-glycoprotein expression levels with patient response to chemotherapy.
- Conducted sequential studies to monitor p-glycoprotein expression changes during and after chemotherapy.
Main Results:
- Substantial p-glycoprotein expression was found in only 1/37 primary melanomas and 1/27 melanoma metastases.
- Patients with negative p-glycoprotein metastases did not respond to chemotherapy.
- One patient with significantly expressing p-glycoprotein metastases achieved complete remission of metastatic growth.
- No significant increase in p-glycoprotein-positive cells was observed during or after chemotherapy.
Conclusions:
- P-glycoprotein-related efflux systems are generally not the primary cause of drug resistance in human melanoma.
- Alternative mechanisms are likely responsible for chemotherapy resistance in this malignancy.