Interleukin-4 stimulates papillary thyroid cancer cell survival: Implications in patients with thyroid cancer and concomitant Graves' disease

Veronica Vella, Rossana Mineo, Francesco Frasca, Emanuela Mazzon, Giuseppe Pandini, Riccardo Vigneri, Antonino Belfiore

Research output: Contribution to journalArticle


IL-4, a pleiotropic cytokine mainly produced by activated helper T lymphocytes type 2 (Th2), is known to protect thyroid cells from autoimmune damage. Acting via its receptors (IL-4Rα), IL-4 has antiproliferative and apoptotic effects in many malignancies. Its effect in thyroid cancer is unknown. We found that surgical specimens of thyroid carcinomas express both IL-4Rα and IL-4 in the majority of cases. Thyroid glands affected by Graves' disease also express IL-4. We also studied a panel of eight thyroid cancer cell lines from different histotypes and found that thyroid cancer cells express high levels of IL-4Rα although they do not express IL-4. We then compared the biological effects of IL-4 in TPC-1, a thyroid cancer cell line, and in MCF-7 breast cancer cells. IL-4 very weakly stimulated thyroid cancer cell proliferation, but it was very effective in protecting thyroid cancer cells from apoptosis induced by staurosporin. The protective effect of IL-4 was similar in magnitude to that of IGF-I and was associated with up-regulation of the antiapoptotic molecule Bcl-2 and weak down-regulation of the proapoptotic molecule Bax. Moreover, IL-4 slightly potentiated the survival effect of IGF-I. In contrast, IL-4 reduced growth and induced apoptosis in MCF-7 cells. Taken together, these findings suggest that thyroid cancer cells receive significant protection from apoptosis by IL-4 produced in the thyroid gland by activated T lymphocytes when concomitant Graves' disease is present.

Original languageEnglish
Pages (from-to)2880-2889
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
Publication statusPublished - Jun 2004


ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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