Membrane transport of methotrexate in a squamous carcinoma cell line adapted to low folate concentrations

B F van der Laan, G Jansen, J A van Gestel, J H Schornagel, G J Hordijk

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Abstract

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.

Original languageEnglish
Pages (from-to)1265-8
Number of pages4
JournalAnticancer Research
Volume11
Issue number3
Publication statusPublished - 1 May 1991

Cite this

van der Laan, B. F., Jansen, G., van Gestel, J. A., Schornagel, J. H., & Hordijk, G. J. (1991). Membrane transport of methotrexate in a squamous carcinoma cell line adapted to low folate concentrations. Anticancer Research, 11(3), 1265-8.