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The critical role of alpha-folate receptor in the resistance of melanoma to methotrexate
Article first published online: 2 JUN 2009
DOI: 10.1111/j.1755-148X.2009.00586.x
© 2009 John Wiley & Sons A/S
Additional Information
How to Cite
Sánchez-del-Campo, L., Montenegro, M. F., Cabezas-Herrera, J. and Rodríguez-López, J. N. (2009), The critical role of alpha-folate receptor in the resistance of melanoma to methotrexate. Pigment Cell & Melanoma Research, 22: 588–600. doi: 10.1111/j.1755-148X.2009.00586.x
Publication History
- Issue published online: 26 AUG 2009
- Article first published online: 2 JUN 2009
- PUBLICATION DATA Received 16 February 2009, revised and accepted for publication 19 May 2009
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Keywords:
- melanoma;
- folate receptor-α;
- methotrexate;
- antifolate resistance;
- (anti)folate transport
Summary
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.