Impairment of methotrexate transport is common in osteosarcoma tumor samples Journal Article

   


Authors: Gorlick, R.; Sowers, R.; Wenzel, B. D.; Richardson, C.; Meyers, P. A.; Healey, J. H.; Levy, A. S.
Article Title: Impairment of methotrexate transport is common in osteosarcoma tumor samples
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. © 2011 Rebecca Sowers et al.
Keywords: osteosarcoma; controlled study; human tissue; human cell; major clinical study; dose response; methotrexate; protein function; fluorescent dye; cancer resistance; drug transport; lysine; transport kinetics; trimetrexate; reduced folate carrier
Journal Title: Sarcoma
Volume: 2011
ISSN: 1357-714X
Publisher: Hindawi Publishing Corporation  
Date Published: 2011-01-01
Start Page: 834170
Language: English
DOI: 10.1155/2011/834170
PROVIDER: scopus
PMCID: PMC3017953
PUBMED: 21234348
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-79952224363&partnerID=40&md5=ef460ed846c2eeb9009d371afb6f7e83
Notes: --- - "Export Date: 23 June 2011" - "Art. No.: 834170" - "CODEN: SARCF" - "Source: Scopus"
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MSK Authors
  1. Paul Meyers
    311 Meyers
  2. John H Healey
    550 Healey
  3. Bethanne Dorothy Wenzel
    20 Wenzel
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