interleukin-8 and Adenocarcinoma--Follicular

The role of nuclear factor (NF)-кBp65 pathway in the pathogenesis of follicular thyroid carcinoma (FTC) has not been fully investigated. We retrieved 10 cases of FTC from our file. Tissue microarrays (TMAs) were constructed using 2.0 mm cores from formalin-fixed, paraffin-embedded tissue blocks. TMA sections were immunohistochemically stained for phosphorylated (p)-NF-кBp65 (Ser 536), cyclooxygenase-2 (COX-2), IL-8, and glutathione S-transferase (GST)-pi. Staining intensity (0-3+), extensiveness (0-100%) and subcellular compartmentalization were evaluated. Both nuclear and cytoplasmic immunoreactivities with p-NF-кBp65 (Ser 536) antibodies were observed in all 10 cases, including moderate to strong nuclear staining intensity with a range of extensiveness in 20% - 100% of tumor cells. Moderate (2+) or strong (3+) cytoplasmic expressions of COX-2 and IL-8 were present in 60-100% and 50- 100% of tumor cells, respectively, in all cases. GST-pi was diffusely (70-100%) and moderately or strongly staining the tumor cytoplasm in all cases (except one case with insufficient tissue) with three of them demonstrating nuclear positivity as well. Morphoproteomic analysis reveals the constitutive activation of the NF-кBp65 pathway in follicular thyroid carcinomas as evidenced by phosphorylation at Ser 536 with nuclear translocation and with correlative expression of transcriptionally activated gene products (COX-2, IL-8, and GST-pi). This observation may provide a molecular basis for the tumor biology and targeted therapies for follicular thyroid carcinoma.

Topics: Adenocarcinoma, Follicular; Cell Nucleus; Cyclooxygenase 2; Cytoplasm; Glutathione S-Transferase pi; Humans; Immunohistochemistry; Interleukin-8; Phosphorylation; Proteomics; Serine; Signal Transduction; Texas; Thyroid Neoplasms; Tissue Array Analysis; Transcription Factor RelA

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 that were used as a control. In the thyroid carcinoma cell line 1736, EGF and bFGF stimulated ATX mRNA expression, whereas the cytokines IL-4, IL-1beta and TGF-beta reduced ATX transcriptional levels. FTC-133 cells, stably transfected with an expression vector for ATX, showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behavior. 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. We conclude that ATX may be regarded as a new tissue marker for undifferentiated human thyroid carcinoma cells. ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Further studies are needed to provide insight into the role of ATX in the normal and neoplastic thyroid gland.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Glucose-6-Phosphate Isomerase; Glycoproteins; Goiter; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-4; Interleukin-8; Male; Middle Aged; Multienzyme Complexes; Phosphodiesterase I; Phosphoric Diester Hydrolases; Pyrophosphatases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Neoplasms; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured