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Related Experiment Videos

Folate and antifolate cell binding and accumulation at physiologic folate concentrations.

B A Kamen1

  • 1Department of Pediatrics, University of Texas Southwestern Medical School, Dallas 75235.

NCI Monographs : a Publication of the National Cancer Institute
|January 1, 1987
PubMed
Summary

Cells utilize a high-affinity folate receptor for nutrient uptake, especially under low folate conditions. This receptor, crucial for cellular folate transport, may serve as a target for new cancer therapies.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Medicine

Background:

  • Cellular folate transport traditionally viewed as carrier-mediated or facilitated diffusion.
  • Previous studies used high folic acid concentrations, potentially masking other mechanisms.
  • Folate is essential for cell growth and DNA synthesis.

Purpose of the Study:

  • To investigate folate uptake mechanisms in folate-depleted cells.
  • To identify and characterize the folate receptor involved in cellular uptake.
  • To explore the potential of this receptor as a therapeutic target.

Main Methods:

  • Culturing cells in folate-depleted medium.
  • Measuring folate binding affinities using various folate derivatives and inhibitors.

Related Experiment Videos

  • Utilizing antisera against folate-binding protein (FBP) to block folate cell binding.
  • Assessing the effect of methyltetrahydrofolate incubation on intracellular folate levels and membrane binding.
  • Main Results:

    • Folate-depleted cells exhibited significant high-affinity folate membrane receptor expression.
    • Dissociation constants indicated high affinity for folic acid (0.4 nM) and 5-methyltetrahydrofolate (4 nM).
    • Receptor-mediated uptake was confirmed, with physiological folate concentrations restoring intracellular levels and reducing membrane binding.

    Conclusions:

    • A high-affinity folate receptor mediates cellular folate uptake, functioning at physiological concentrations.
    • This receptor is distinct from simple diffusion or carrier-mediated transport.
    • The folate receptor represents a potential novel membrane target for antifolate and antineoplastic agents.