The critical role of alpha‐folate receptor in the resistance of melanoma to methotrexate |
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Authors: | Luís Sánchez‐del‐Campo María F Montenegro Juan Cabezas‐Herrera José Neptuno Rodríguez‐López |
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Institution: | 1. Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Murcia, Spain;2. Research Unit of Clinical Analysis Service, University Hospital Virgen de la Arrixaca, Murcia, Spain |
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Abstract: | Although methotrexate (MTX) is an effective drug for several types of cancer, it is not active against melanoma. Experiments following methotrexate treatment indicated a reduced accumulation of the drug in the cytosolic compartment in melanoma cells, suggesting that the mechanisms that control the transport and retention of this drug could be altered in melanoma. For this reason, we analyzed the presence and function of folate receptor‐α (FRα) in melanoma cells. In this study, we have identified the presence of FRα in normal and pathological melanocytes and demonstrated that MTX is preferentially transported through this receptor in melanoma cells. FRα‐induced endocytic transport of MTX, together with drug melanosomal sequestration and cellular exportation, ensures reduced accumulation of this cytotoxic compound in intracellular compartments. The critical role of FRα in this mechanism of resistance and the therapeutic consequences of these findings are also discussed. |
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Keywords: | melanoma folate receptor‐α methotrexate antifolate resistance (anti)folate transport |
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