Membrane transport of methotrexate in a squamous carcinoma cell line adapted to low folate concentrations.
Membrane transport characteristics of the folate analogue methotrexate (MTX) were studied in a human squamous carcinoma cell line of the head and neck (HNSCC) adapted to grow in tissue culture media with nanomolar reduced folate concentrations (SCC-11B-LF), as compared to SCC-11B cells grown in standard medium containing high folate concentrations. We observed that SCC-11B-LF cells exhibited a 10.5-fold increased uptake of [3H]-MTX via the reduced folate/MTX carrier system compared to SCC-11B cells. Affinity labelling of the reduced folate/MTX carrier system suggests that the up-regulation of [3H]-MTX transport mainly results from an increased rate of carrier translocation, and only to a minor extent (15-20%) from an increased amount of carrier protein. The upregulation of MTX transport resulted in a 2.4-fold increased growth inhibitory effect by MTX. These results suggest that membrane transport may play a more important role in MTX-cytotoxicity when SCC-11B cells in vitro are grown in more physiological folate concentrations.
van der Laan
B F
BF
Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital Utrecht, The Netherlands.
Jansen
G
G
van Gestel
J A
JA
Schornagel
J H
JH
Hordijk
G J
GJ
D000222:Adaptation, Physiological; D001692:Biological Transport; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005492:Folic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D005492:Folic Acid; D008727:Methotrexate