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Folate is an essential vitamin that must be obtained from food intake through intestinal absorption in mammals. Folate and reduced folic acid derivatives bind to the folate receptor (FR) family, which mediates the endocytosis of 5-methyltetrahydrofolate into the cell. The folate receptors consist of five members, alpha, beta, gamma, gamma' (which is produced by alternative splicing) and delta. beta-FR is attached to the membrane by a GPI anchor and is expressed in malignant tissues of epithelial and nonepithelial origin. gamma-FR is expressed in tissues of hematopoietic origin, such as spleen, thymus and bone marrow. The expression pattern of delta-FR is elusive, which suggests that it is highly restricted both spatially and temporally. The alpha isoform of the folate receptor is used as a highly selective tumor marker and may be targeted for the delivery of therapeutic compounds to tumor cells by coupling to derivatives of folic acid.
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