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Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines.

Publication ,  Journal Article
Li, WW; Lin, JT; Schweitzer, BI; Tong, WP; Niedzwiecki, D; Bertino, JR
Published in: Cancer Res
July 15, 1992

A human fibrosarcoma cell line, HT-1080, and four new cell lines (HS-16, HS-28, HS-30, and HS-42) were established from untreated patients with mesenchymal chondrosarcoma, peripheral nerve sheath sarcoma, malignant hemangiopericytoma, and mixed mesodermal tumor, respectively, and were used for analysis of mechanisms of intrinsic resistance to methotrexate. All four new cell lines were resistant to methotrexate as determined by inhibition of thymidylate synthase in whole cells and by growth inhibition, as compared with HT-1080, a methotrexate sensitive cell line. Methotrexate uptake, level of dihydrofolate reductase, and inhibition of this enzyme by methotrexate in the four cell lines were comparable to HT-1080 cells. However, levels of long chain polyglutamates (glu3-5) of methotrexate achieved after a 24-h incubation with this drug were much lower in the four new cell lines as compared to the HT-1080 cell line (5- to 20-fold lower). The low levels of methotrexate polyglutamates formed is likely the major cause of intrinsic methotrexate resistance in these new sarcoma cell lines.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 15, 1992

Volume

52

Issue

14

Start / End Page

3908 / 3913

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Trimetrexate
  • Tetrahydrofolate Dehydrogenase
  • Soft Tissue Neoplasms
  • Sarcoma
  • Polyglutamic Acid
  • Peptide Synthases
  • Oncology & Carcinogenesis
  • Methotrexate
  • Humans
 

Citation

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MLA
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Li, W. W., Lin, J. T., Schweitzer, B. I., Tong, W. P., Niedzwiecki, D., & Bertino, J. R. (1992). Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines. Cancer Res, 52(14), 3908–3913.
Li, W. W., J. T. Lin, B. I. Schweitzer, W. P. Tong, D. Niedzwiecki, and J. R. Bertino. “Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines.Cancer Res 52, no. 14 (July 15, 1992): 3908–13.
Li WW, Lin JT, Schweitzer BI, Tong WP, Niedzwiecki D, Bertino JR. Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines. Cancer Res. 1992 Jul 15;52(14):3908–13.
Li, W. W., et al. “Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines.Cancer Res, vol. 52, no. 14, July 1992, pp. 3908–13.
Li WW, Lin JT, Schweitzer BI, Tong WP, Niedzwiecki D, Bertino JR. Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines. Cancer Res. 1992 Jul 15;52(14):3908–3913.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 15, 1992

Volume

52

Issue

14

Start / End Page

3908 / 3913

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Trimetrexate
  • Tetrahydrofolate Dehydrogenase
  • Soft Tissue Neoplasms
  • Sarcoma
  • Polyglutamic Acid
  • Peptide Synthases
  • Oncology & Carcinogenesis
  • Methotrexate
  • Humans