Impairment of methotrexate transport is common in osteosarcoma tumor samples

Richard Gorlick, Rebecca Sowers, Bethanne D. Wenzel, Condon Richardson, Paul A. Meyers, John H. Healey, Adam S. Levy

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored.

Original languageEnglish (US)
Article number834170
JournalSarcoma
Volume2011
DOIs
StatePublished - 2011

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Osteosarcoma
Methotrexate
Reduced Folate Carrier Protein
Trimetrexate
Folic Acid Antagonists
Cell Membrane

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Gorlick, R., Sowers, R., Wenzel, B. D., Richardson, C., Meyers, P. A., Healey, J. H., & Levy, A. S. (2011). Impairment of methotrexate transport is common in osteosarcoma tumor samples. Sarcoma, 2011, [834170]. https://doi.org/10.1155/2011/834170

Impairment of methotrexate transport is common in osteosarcoma tumor samples. / Gorlick, Richard; Sowers, Rebecca; Wenzel, Bethanne D.; Richardson, Condon; Meyers, Paul A.; Healey, John H.; Levy, Adam S.

In: Sarcoma, Vol. 2011, 834170, 2011.

Research output: Contribution to journalArticle

Gorlick, R, Sowers, R, Wenzel, BD, Richardson, C, Meyers, PA, Healey, JH & Levy, AS 2011, 'Impairment of methotrexate transport is common in osteosarcoma tumor samples', Sarcoma, vol. 2011, 834170. https://doi.org/10.1155/2011/834170
Gorlick R, Sowers R, Wenzel BD, Richardson C, Meyers PA, Healey JH et al. Impairment of methotrexate transport is common in osteosarcoma tumor samples. Sarcoma. 2011;2011. 834170. https://doi.org/10.1155/2011/834170
Gorlick, Richard ; Sowers, Rebecca ; Wenzel, Bethanne D. ; Richardson, Condon ; Meyers, Paul A. ; Healey, John H. ; Levy, Adam S. / Impairment of methotrexate transport is common in osteosarcoma tumor samples. In: Sarcoma. 2011 ; Vol. 2011.
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