期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 22, 期 5, 页码 588-600出版社
WILEY
DOI: 10.1111/j.1755-148X.2009.00586.x
关键词
melanoma; folate receptor-alpha; methotrexate; antifolate resistance; (anti)folate transport
资金
- Ministerio de Ciencia e Innovacion [SAF2006-07040-C02-01, SAF2006-07040-C02-02]
- Conserjeria de Educacion, Ciencia e Investigacion (Comunidad Autonoma de Murcia) [BIO-BMC 07/03-009]
P>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-alpha (FR alpha) in melanoma cells. In this study, we have identified the presence of FR alpha in normal and pathological melanocytes and demonstrated that MTX is preferentially transported through this receptor in melanoma cells. FR alpha-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 FR alpha in this mechanism of resistance and the therapeutic consequences of these findings are also discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据