A novel folate transport activity in human mesothelioma cell lines with high affinity and specificity for the new-generation antifolate, pemetrexed.

Abstract	Pemetrexed is a novel antifolate effective in the treatment of mesothelioma. Studies were undertaken to characterize the transport of this antifolate in this tumor. We report the presence of a novel, concentrative high-affinity transport activity in three human mesothelioma cell lines, characterized in detail in the NCI-H28 line, with a pemetrexed influx K(t) of 30 nM and V(max) of 10 nmol/g protein/min. This route is highly specific for pemetrexed, with a substrate specificity pattern quite different from that of the reduced folate carrier and folate receptors. In particular, there is an apparent relatively low affinity for other antifolate inhibitors of dihydrofolate-reductase (MTX, aminopterin, PT523) and thymidylate synthase (ZD1694, ZD9331). Besides its impact on the transport of pemetrexed, this high-affinity route may represent another pathway by which physiological folates are transported into human cells.
Authors	Yanhua Wang, Rongbao Zhao, Shrikanta Chattopadhyay, I David Goldman
Journal	Cancer research (Cancer Res) Vol. 62 Issue 22 Pg. 6434-7 (Nov 15 2002) ISSN: 0008-5472 [Print] United States
PMID	12438230 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antineoplastic Agents Carrier Proteins DNA, Complementary Folate Receptors, GPI-Anchored Folic Acid Antagonists Glutamates Membrane Transport Proteins Receptors, Cell Surface Reduced Folate Carrier Protein SLC19A1 protein, human Pemetrexed Guanine Methotrexate
Topics	Antineoplastic Agents (pharmacokinetics) Biological Transport Carrier Proteins (genetics, metabolism) DNA, Complementary (genetics) Folate Receptors, GPI-Anchored Folic Acid Antagonists (pharmacokinetics) Glutamates (pharmacokinetics) Guanine (analogs & derivatives, pharmacokinetics) Humans Membrane Transport Proteins Mesothelioma (metabolism) Methotrexate (pharmacokinetics) Pemetrexed Receptors, Cell Surface Reduced Folate Carrier Protein Substrate Specificity Tumor Cells, Cultured

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