Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines Journal Article

  


Authors: Li, W. W.; Lin, J. T.; Schweitzer, B. I.; Tong, W. P.; Niedzwiecki, D.; Bertino, J. R.
Article Title: Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines
Abstract: 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 mesoderma! tu mor, 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 reducãase, 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. © 1992, American Association for Cancer Research. All rights reserved.
Keywords: controlled study; human cell; methotrexate; enzyme inhibition; antineoplastic activity; drug resistance; tumor cells, cultured; sarcoma; cancer inhibition; soft tissue sarcoma; hemangiopericytoma; dihydrofolate reductase; thymidylate synthase; tetrahydrofolate dehydrogenase; nerve sheath tumor; chondrosarcoma; soft tissue neoplasms; pleomorphic adenoma; trimetrexate; polyglutamic acid; peptide synthases; human; priority journal; article; support, u.s. gov't, p.h.s.
Journal Title: Cancer Research
Volume: 52
Issue: 14
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1992-07-15
Start Page: 3908
End Page: 3913
Language: English
PUBMED: 1377601
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026653864&partnerID=40&md5=45233f56351e3f848a36fd964a070298
Notes: Article -- Export Date: 30 July 2019 -- Source: Scopus
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MSK Authors
  1. Weiwei Li
    63 Li
  2. William Ping-Yiu Tong
    158 Tong
  3. Joseph Bertino
    363 Bertino
  4. Donna Niedzwiecki
    61 Niedzwiecki
  5. Barry I. Schweitzer
    22 Schweitzer
  6. James T. Lin
    14 Lin
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