Folate receptors
- PMID: 8839936
- DOI: 10.1146/annurev.nu.16.070196.002441
Folate receptors
Abstract
Glycosyl-phosphatidylinositol-anchored folate receptors (FR) have physiologic and pharmacologic relevance in mediating cellular and transcellular folate/antifolate transport. Three FR isoforms with differing relative affinities for folates and expression patterns in normal and malignant cells/tissues are recognized, but the precise mechanism of cellular entry of folate via FR remains controversial. Although FR expression allows previously FR-deficient cells to survive a reduced folate milieu, an inverse relationship between FR expression and cell proliferation has been established in some cells. The inverse regulation of FR expression by the extracellular folate concentration suggests heterogeneity in underlying mechanisms. Whereas reduced FR expression is yet another mechanism for acquiring antifolate resistance, overexpression of FR does not invariably render cells more sensitive to antifolates. The exploitation of FRs as Trojan horses to deliver folate-tagged liposomes bearing diverse cargo represents a novel therapeutic strategy to target FR-expressing cells. Finally, a critically important role of human placental FR in mediating maternal-to-fetal transplacental transport of folates has been established. Thus, FR appear to have a major impact on several aspects of human physiology and medicine.
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