MULTIDRUG RESISTANCE-RELATED PROTEINS IN PRIMARY CHOROIDAL MELANOMAS AND IN-VITRO CELL-LINES

Purpose. Metastatic uveal melanoma is strongly resistant to chemothera py, and multidrug resistance (MDR) may be involved. To investigate the role of MDR, the presence of the MDR-associated proteins P-glycoprote in (Pgp), MRP, and lung resistance protein (LRP) was determined on pri mary choroidal melanomas and cell lines. Methods. A panel of primary c horoidal melanomas was examined for the presence of MD-associated prot eins by immunohistochemical analysis. In cell lines established from f our primary choroidal melanomas and one metastatic choroidal melanoma, the expression of MDR associated proteins was determined with monoclo nal antibodies in cytospin preparations and flow cytometry. In additio n, the functional capacities of transporter proteins Pgp and MRP as ad enosine triphosphate-driven efflux pumps were determined by measuring the cellular accumulation and efflux of the fluorescent dyes rhodamine 123 and calcein-AM, with and without the presence of specific pump in hibitors PSC833 and probenecid. Results. Low levels of Pgp and MRP wer e detected in most primary tumors and in some cell lines. Measurable t ransporter function of Pgp could be determined in cell line OCM-1. Lun g-resistance protein was present in all primary tumors and cell lines and showed high expression levels. Conclusions. This study revealed th e involvement of LRP and at least a minor role of Pgp and MRP in chemo resistance of choroidal melanoma. Compared with cutaneous melanomas, u veal melanomas appear to express slightly higher levels of Pgp. These findings provide insights into the drug-resistant phenotype of this di sease and can aid in the design of therapeutic protocols.