Tumor Biology

, Volume 37, Issue 4, pp 5569–5575 | Cite as

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
Original Article


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.


Thyroid cancer Chemokine receptor CCR6 Tumor necrosis factor-α Thyroid cancer cell lines 


Compliance with ethical standards

Conflicts of interest


Funding statements

The present study received no funding.

Consent to participate

Signed informed consent was obtained from all patients.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Francesca Coperchini
    • 1
  • Patrizia Pignatti
    • 2
  • Andrea Carbone
    • 1
  • Rossana Bongianino
    • 3
  • Christian A. Di Buduo
    • 4
    • 5
  • Paola Leporati
    • 1
  • Laura Croce
    • 1
  • Flavia Magri
    • 1
  • Alessandra Balduini
    • 4
    • 5
    • 6
  • Luca Chiovato
    • 1
  • Mario Rotondi
    • 1
  1. 1.Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine DisruptorsFondazione Salvatore Maugeri I.R.C.C.S.PaviaItaly
  2. 2.Allergy and Immunology UnitFondazione Salvatore Maugeri I.R.C.C.S.PaviaItaly
  3. 3.Molecular Cardiology UnitFondazione Salvatore Maugeri I.R.C.C.S.PaviaItaly
  4. 4.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  5. 5.Biotechnology Research LaboratoriesIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo FoundationPaviaItaly
  6. 6.Department of Biomedical EngineeringTufts UniversityMedfordUSA

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