Medroxyprogesterone acetate decreases secretion of interleukin-6 and parathyroid hormone-related protein in a new anaplastic thyroid cancer cell line, KTC-2.
A new thyroid cancer cell line, KTC-2, was established from the malignant pleural effusion of a patient with recurrent thyroid cancer associated with anaplastic transformation from thyroid papillary cancer. Karyotype analysis showed a mode of 109 chromosomes. Subcutaneous cell injections produced small regressing tumors in athymic or severe combined immunodeficiency disorders (SCID) mice. Histologic examination showed anaplastic tumor cells surrounded by prominent mononuclear cells. An expression of thyroglobulin, thyroid transcription factor-1, and PAX-8 but not thyroid peroxidase and thyrotropin (TSH) receptor was detected. Biochemical analysis revealed secretion of interleukin (IL)-6, parathyroid hormone-related protein (PTHrP), and granulocyte-macrophage colony-stimulating factor. All the cytokines are known to induce paraneoplastic syndromes in patients with anaplastic thyroid cancer. Our previous studies revealed that medroxyprogesterone acetate (MPA) reduces secretion of IL-6 and PTHrP from human breast cancer cells. To investigate the regulatory mechanisms of secretion of these cytokines, MPA was administered to the KTC-2 cells. MPA dose-dependently decreased the secretion and mRNA expression of IL-6 and PTHrP. Expression of androgen receptor and glucocorticoid receptor (GR) but not progesterone receptor was detected. Dexamethasone but not dihydrotestosterone and progesterone decreased IL-6 and PTHrP secretion. These findings suggest that MPA decreases IL-6 and PTHrP secretion as a glucocorticoid mediated by GR in the KTC-2 cells. This KTC-2 cell line may be a suitable model for developing new strategies against paraneoplastic syndromes caused by anaplastic thyroid cancer.
Kurebayashi
Junichi
J
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, Japan. kure@med.kawasaki-m.ac.jp
Otsuki
Takemi
T
Tanaka
Katsuhiro
K
Yamamoto
Yutaka
Y
Moriya
Takuya
T
Sonoo
Hiroshi
H
D002291:Carcinoma, Papillary / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008858:Microscopy, Phase-Contrast; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012636:Secretory Rate / Q000187:drug effects; D013954:Thyroglobulin / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D017931:DNA Primers; D015850:Interleukin-6; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D011374:Progesterone; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013954:Thyroglobulin; D017258:Medroxyprogesterone Acetate