Impairment of methotrexate transport is common in osteosarcoma tumor samples Academic Article uri icon

Overview

MeSH Major

  • Osteosarcoma
  • Receptor, Parathyroid Hormone, Type 1

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.

publication date

  • March 8, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3017953

Digital Object Identifier (DOI)

  • 10.1155/2011/834170

PubMed ID

  • 21234348

Additional Document Info

start page

  • 834170

volume

  • 2011