TNF-α increases the membrane expression of the chemokine receptor CCR6 in thyroid tumor cells, but not in normal thyrocytes: potential role in the metastatic spread of thyroid cancer

Francesca Coperchini, Patrizia Pignatti, Andrea Carbone, Rossana Bongianino, Christian A Di Buduo, Paola Leporati, Laura Croce, Flavia Magri, Alessandra Balduini, Luca Chiovato, Mario Rotondi

Research output: Contribution to journalArticle

Abstract

The chemokine receptor CCR6, selectively bound by CCL20, is involved in the metastatic spread of cancer cells. Tumor necrosis factor-α (TNF-α) displays a complex pro-tumorigenic actions, but it is unknown whether this cytokine could modulate the expression of chemokine receptors in thyroid tumors. The membrane expression of CCR6 was assessed by flow cytometry and immunofluorescence, in primary cultures of normal human thyroid (NHT) cells and in thyroid cancer cell lines (TPC-1 and BCPAP), both in basal conditions and after stimulation with TNF-α. In basal conditions, CCR6+ cells were virtually absent in NHT cells (0.4 ± 0.4 %), while they were detected in TPC-1 (23.6 ± 6.6 %) and in BCPAP (12.9 ± 9.4 %) tumor cells (ANOVA F: 10.534; p < 0.005). The incubation with TNF-α significantly increased the percentage of CCR6+ cells in TPC-1 (23.6 ± 6.6 % vs. 33.1 ± 8.7; p < 0.033) and in BCPAP (12.9 ± 9.4 % vs. 18.1 ± 11.5; p < 0.030), but not in NHT (0.4 ± 0.4 % vs. 0.2 ± 0.3; NS) cells. The magnitude of the TNF-α effect was similar for TPC-1 and BCPAP (∼40 % vs. baseline) cells. TPC-1 cells were characterized by a greater amount of CCR6 per cell as compared with BCPAP cells, both in basal conditions (148.3 ± 33.7 fluorescence intensity vs. 102.5 ± 22.1 p < 0.016) and after TNF-α stimulation (147.8 ± 46.3 fluorescence intensity vs. 95.3 ± 18.5; p < 0.025). Cell migration assays showed that TNF-α treatment significantly increased the rate of migrated cells in those cells in which it also increased the membrane expression of CCR6 (TPC-1 and BCPAP) as compared to basal condition (p < 0.05 for both TPC-1 and BCPAP cells). No effect was observed in NHT cells in which TNF-α stimulation had no effect in terms of CCR6 expression. We first report that TNF-α enhances the expression of CCR6 in thyroid tumor cells, thus providing evidence that TNF-α increases the metastatic potential of thyroid tumors.

Original languageEnglish
Pages (from-to)5569-75
Number of pages7
JournalTumor Biology
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2016

Keywords

  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CCL20
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Receptors, CCR6
  • Thyroid Epithelial Cells
  • Thyroid Gland
  • Thyroid Neoplasms
  • Tumor Necrosis Factor-alpha
  • Journal Article

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