Autotaxin is linked with differential gene expression of IL-8, ICAM/CD54 and the tumor-associated antigen GAGE in thyroid carcinomas

Autotaxin (ATX/NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/ phosphodiesterase activity and a recently described lysophospholipase D (lysoPLD) activity. The precise function of ATX in tumor cells and the role of ATX in thyroid carcinoma remains unclear. We have quantified ATX mRNA expression in thyroid carcinoma cell lines and in tissues of patients with thyroid carcinomas. ATX gene activity was significantly higher in undifferentiated anaplastic thyroid carcinoma cell lines (UTC) and tumor tissues as compared to follicular thyroid carcinoma (FTC) cell lines, FTC tissues or goiter tissues used as a control. FTC-133 or -238 cells stably transfected with an expression vector for ATX showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behaviour. In addition, ATX also displayed a paracrine stimulatory effect on the motility of different thyroid carcinoma cell lines. Overexpression of ATX in the stably transfected FTC-133 resulted in down-regulation of CD54/ intercellular adhesion molecule-1 (ICAM-1) gene expression and augmented gene activity of the pro-angiogenic chemokine IL-8. In FTC-133 cells ATX expression resulted in a decrease of the tumor-associated antigen GAGE whereas in FTC-238 cells ATX is associated with an augmented GAGE expression.

We conclude that ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Furthermore, ATX showed a cell type-specific effect on the expression of the tumor-associated antigen GAGE.