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Expression, regulation and function of autotaxin in thyroid carcinomas

Astrid Kehlen1, Nadine Englert, Anja Seifert

  • 1Institute of Medical Immunology, University of Halle-Wittenberg, Halle, Germany. astrid.kehlen@medizin.uni-halle.de

International Journal of Cancer
|March 18, 2004
PubMed

Insights

Autotaxin (ATX) is elevated in anaplastic thyroid carcinoma, promoting tumor cell proliferation, migration, and potentially angiogenesis. This suggests ATX could serve as a marker for aggressive thyroid cancers.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Autotaxin (ATX/NPP2) is a secreted enzyme with nucleotide pyrophosphatase/phosphodiesterase and lysophospholipase D activities.
  • ATX is known to stimulate tumor cell motility, but its specific role in thyroid carcinoma remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression and function of ATX in various types of thyroid carcinoma.
  • To determine the potential of ATX as a diagnostic marker and therapeutic target in thyroid cancer.

Main Methods:

  • Quantification of ATX mRNA expression in thyroid carcinoma cell lines and patient tissues.
  • Stimulation of ATX expression using growth factors and cytokines.
  • Stable transfection of thyroid carcinoma cells to overexpress ATX.
  • Assessment of cell proliferation, migration, and gene expression changes (CD54, IL-8) in response to ATX modulation.

Main Results:

  • ATX mRNA expression was significantly higher in undifferentiated anaplastic thyroid carcinoma (UTC) compared to follicular thyroid carcinoma (FTC) and goiter tissues.
  • Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) increased ATX mRNA, while IL-4, IL-1beta, and TGF-beta decreased it.
  • Overexpression of ATX in FTC cells led to increased proliferation, migration, lysophospholipase D activity, and paracrine motility stimulation.
  • ATX overexpression downregulated CD54/ICAM-1 and upregulated pro-angiogenic IL-8 gene expression.

Conclusions:

  • ATX is a potential tissue marker for undifferentiated human thyroid carcinoma.
  • ATX enhances thyroid carcinoma cell proliferation and migration and may influence tumor angiogenesis.
  • Further research is warranted to elucidate the comprehensive role of ATX in thyroid gland physiology and pathology.

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