The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells

  • Authors:
    • Anja Seifert
    • Thomas Klonisch
    • Jens Wulfaenger
    • Friedrich Haag
    • Henning Dralle
    • Jürgen Langner
    • Cuong Hoang-Vu
    • Astrid Kehlen
  • View Affiliations

  • Published online on: June 1, 2008     https://doi.org/10.3892/or.19.6.1485
  • Pages: 1485-1491
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Abstract

Autotaxin (ATX/NPP2) shows a nucleotide pyrophosphatase/phosphodiesterase and lysophospholipase D (lysoPLD) activity and is a member of a family of structurally-related mammalian ecto-nucleotide pyrophosphate/phosphodiesterases (E-NPP1-3). ATX is unique among E-NPP as it is secreted and not membrane-bound as are NPP1 and -3. The ATX gene activity is significantly higher in undifferentiated anaplastic (UTC) as compared to follicular (FTC) and papillary thyroid carcinomas (PTC) or goiter tissues. ATX also enhances the motility of thyroid tumor cells. We bio-engineered stable transfectants of the human thyroid carcinoma cell line FTC-238 expressing either bioactively-secreted (sATX) or membrane-anchored ATX (mATX) to identify the biological functions of ATX which critically depend on the E-NPP member being secreted and provide insight into the effects of high local ATX concentrations and cellular responses. An increased cell motility was exclusively observed with FTC-238 sATX transfectants, whereas membrane-anchored ATX appeared to impair motility. We identified IL-1β as an upstream suppressor of ATX expression in FTC-238, ATX-mediated motility in FTC-238 and stable transfectants, with IL-1β having the strongest motility-suppressive effect on FTC-238 sATX clones. sATX and mATX strongly increased the anchorage-independent colony formation of FTC-238 but the size and number of colonies formed in the soft agar were significantly smaller in FTC-238 mATX versus the FTC-238 sATX clones. The cancer-testis antigen BAGE was identified as a novel target gene of ATX in FTC-238. Transcript levels for BAGE were 6-fold higher in FTC-238 mATX versus sATX clones. Increased BAGE transcript levels were also detected in tissues of patients with UTC versus FTC, PTC or goiter tissues. In summary, enhanced tumor cell motility and tumorigenic capacity critically depended on sATX in thyroid carcinoma cells. Irrespective of its compartmentalization, the cancer-testis antigen BAGE was identified as a novel target gene of ATX in FTC-238 and a potential new tissue marker in UTC tissues, which we had previously shown to express high levels of ATX.

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June 2008
Volume 19 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Seifert A, Klonisch T, Wulfaenger J, Haag F, Dralle H, Langner J, Hoang-Vu C and Kehlen A: The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells. Oncol Rep 19: 1485-1491, 2008
APA
Seifert, A., Klonisch, T., Wulfaenger, J., Haag, F., Dralle, H., Langner, J. ... Kehlen, A. (2008). The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells. Oncology Reports, 19, 1485-1491. https://doi.org/10.3892/or.19.6.1485
MLA
Seifert, A., Klonisch, T., Wulfaenger, J., Haag, F., Dralle, H., Langner, J., Hoang-Vu, C., Kehlen, A."The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells". Oncology Reports 19.6 (2008): 1485-1491.
Chicago
Seifert, A., Klonisch, T., Wulfaenger, J., Haag, F., Dralle, H., Langner, J., Hoang-Vu, C., Kehlen, A."The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells". Oncology Reports 19, no. 6 (2008): 1485-1491. https://doi.org/10.3892/or.19.6.1485