Interleukin-4 stimulates papillary thyroid cancer cell survival: implications in patients with thyroid cancer and concomitant Graves' disease.
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-4Ralpha), 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-4Ralpha 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-4Ralpha 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.
Vella
Veronica
V
Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia, University of Catania, Ospedale Garibaldi, Italy.
Mineo
Rossana
R
Frasca
Francesco
F
Mazzon
Emanuela
E
Pandini
Giuseppe
G
Vigneri
Riccardo
R
Belfiore
Antonino
A
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002291:Carcinoma, Papillary / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006111:Graves Disease / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018418:Th2 Cells / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000150:complications* / Q000473:pathology / Q000503:physiopathology
D019948:Receptors, Interleukin-4; D015847:Interleukin-4