nach oben

Erschienen in:

08.01.2019 | Review

The paramount role of cytokines and chemokines in papillary thyroid cancer: a review and experimental results

verfasst von: Poupak Fallahi, Silvia Martina Ferrari, Simona Piaggi, Michaela Luconi, Giulia Cantini, Stefania Gelmini, Giusy Elia, Ilaria Ruffilli, Alessandro Antonelli

Erschienen in: Immunologic Research | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Our study demonstrates that (C-X-C motif) ligand 9 and 11 (CXCL9, CXCL11) chemokines were absent basally in non-neoplastic thyroid (TFC) and papillary thyroid carcinoma (PTC) cells. Interferon (IFN)γ induced the chemokine secretion in TFC and PTC, while tumor necrosis factor (TNF)α induced it only in PTC. IFNγ+TNFα induced a synergistic chemokines release in PTC, and at a lower level in TFC. Peroxisome proliferator-activated receptor (PPAR)γ agonists suppressed dose-dependently IFNγ+TNFα-induced chemokine release in TFC, while stimulated it in PTC. PPARγ knocking down, by RNA interference technique in PTC cells, abolished the effect of PPARγ agonists on chemokines release. In PTC cells, PPARγ agonists reduced proliferation, and CXCL9 or CXCL11 (100 and 500 pg/mL) reduced proliferation and migration (P < 0.01, for all). In conclusion, in PTC cells: (a) IFNγ+TNFα induced a marked release of CXCL9 and CXCL11; (b) PPARγ agonists stimulated CXCL9 and CXCL11 secretion, while inhibited proliferation; (c) CXCL9 and CXCL11 inhibited proliferation and migration. The use of CXCL9 or CXCL11 as antineoplastic agents in PTC remains to be explored.

Highlights

• IFNγ and IFNγ+TNFα induce dose-dependently CXCL9 (and less CXCL11) in PTC cells.

• Rosi and Pio dose-dependently inhibit the PTC cells proliferation.

• Rosi and Pio (at variance of normal TFC) stimulate CXCL9 or CXCL11 secretion.

• CXCL9 or CXCL11 induce a significant antiproliferative effect in PTC cells.

• Chemokines induced by IFNγ (CXCL9 or CXCL11) inhibit migration in PTC cells.

Soejima K, Rollins BJ. A functional IFN-gamma-inducible protein-10/CXCL10-specific receptor expressed by epithelial and endothelial cells that is neither CXCR3 nor glycosaminoglycan. J Immunol. 2001;167:6576–82.CrossRefPubMed

Kawada K, Sonoshita M, Sakashita H, Takabayashi A, Yamaoka Y, Manabe T, et al. Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res. 2004;64:4010–7.CrossRefPubMed

Suyama T, Furuya M, Nishiyama M, Kasuya Y, Kimura S, Ichikawa T, et al. Up-regulation of the interferon gamma (IFN-gamma)-inducible chemokines IFN-inducible T-cell alpha chemoattractant and monokine induced by IFN-gamma and of their receptor CXC receptor 3 in human renal cell carcinoma. Cancer. 2005;103:258–67.CrossRefPubMed

Mantovani A, Savino B, Locati M, Zammataro L, Allavena P, Bonecchi R. The chemokine system in cancer biology and therapy. Cytokine Growth Factor Rev. 2010;21:27–39.CrossRefPubMed

Melillo RM, Castellone MD, Guarino V, De Falco V, Cirafici AM, Salvatore G, et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest. 2005;115:1068–81 (Retracted Article; Citation for this retraction: J Clin Invest 2016;126:1603).CrossRefPubMedPubMedCentral

Puxeddu E, Knauf JA, Sartor MA, Mitsutake N, Smith EP, Medvedovic M, et al. RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response. Endocr Relat Cancer. 2005;12:319–34.CrossRefPubMed

Antonelli A, Ferrari SM, Fallahi P, Frascerra S, Piaggi S, Gelmini S, et al. Dysregulation of secretion of CXC alpha-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-gamma agonists. Endocr Relat Cancer. 2009;16:1299–311.CrossRefPubMed

McCall KD, Harii N, Lewis CJ, Malgor R, Kim WB, Saji M, et al. High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration. Endocrinology. 2007;148:4226–37.CrossRefPubMed

Antonelli A, Ferrari SM, Giuggioli D, Ferrannini E, Ferri C, Fallahi P. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev. 2014;13:272–80.CrossRefPubMed

10.

Antonelli A, Ferrari SM, Corrado A, Ferrannini E, Fallahi P. CXCR3, CXCL10 and type 1 diabetes. Cytokine Growth Factor Rev. 2014;25:57–65.CrossRefPubMed

11.

Antonelli A, Rotondi M, Fallahi P, Romagnani P, Ferrari SM, Barani L, et al. Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in patients with active Graves' disease, and modulation by methimazole therapy. Clin Endocrinol. 2006;64:189–95.CrossRef

12.

Antonelli A, Rotondi M, Fallahi P, Grosso M, Boni G, Ferrari SM, et al. Iodine-131 given for therapeutic purposes modulates differently interferon-gamma-inducible alpha-chemokine CXCL10 serum levels in patients with active graves’ disease or toxic nodular goiter. J Clin Endocrinol Metab. 2007;92:1485–90.CrossRefPubMed

13.

Antonelli A, Ferrari SM, Fallahi P, Frascerra S, Santini E, Franceschini SS, et al. Monokine induced by interferon gamma (IFNgamma) (CXCL9) and IFNgamma inducible T-cell alpha-chemoattractant (CXCL11) involvement in Graves' disease and ophthalmopathy: modulation by peroxisome proliferator-activated receptor-gamma agonists. J Clin Endocrinol Metab. 2009;94:1803–9.CrossRefPubMed

14.

Antonelli A, Ferrari SM, Mancusi C, Mazzi V, Pupilli C, Centanni M, et al. Interferon-α, −β and -γ induce CXCL11 secretion in human thyrocytes: modulation by peroxisome proliferator-activated receptor γ agonists. Immunobiology. 2013;218:690–5.CrossRefPubMed

15.

Antonelli A, Ferrari SM, Frascerra S, Pupilli C, Mancusi C, Metelli MR, et al. CXCL9 and CXCL11 chemokines modulation by peroxisome proliferator-activated receptor-alpha agonists secretion in Graves' and normal thyrocytes. J Clin Endocrinol Metab. 2010;95:E413–20.CrossRefPubMed

16.

Antonelli A, Ferrari SM, Frascerra S, Galetta F, Franzoni F, Corrado A, et al. Circulating chemokine (CXC motif) ligand (CXCL)9 is increased in aggressive chronic autoimmune thyroiditis, in association with CXCL10. Cytokine. 2011;55:288–93.CrossRefPubMed

17.

Antonelli A, Ferrari SM, Frascerra S, Di Domenicantonio A, Nicolini A, Ferrari P, et al. Increase of circulating CXCL9 and CXCL11 associated with euthyroid or subclinically hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab. 2011;96:1859–63.CrossRefPubMed

18.

Ohta K, Endo T, Haraguchi K, Hershman JM, Onaya T. Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells. J Clin Endocrinol Metab. 2001;86:2170–7.PubMed

19.

Grommes C, Landreth GE, Heneka MT. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet. 2004;5:419–29.CrossRefPubMed

20.

Antonelli A, Ferrari SM, Fallahi P, Berti P, Materazzi G, Marchetti I, et al. Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration. Eur J Endocrinol. 2008;159:283–91.CrossRefPubMed

21.

Antonelli A, Fallahi P, Ferrari SM, Carpi A, Berti P, Materazzi G, et al. Dedifferentiated thyroid cancer: a therapeutic challenge. Biomed Pharmacother. 2008;62:559–63.CrossRefPubMed

22.

Antonelli A, Ferrari SM, Fallahi P, Berti P, Materazzi G, Minuto M, et al. Thiazolidinediones and antiblastics in primary human anaplastic thyroid cancer cells. Clin Endocrinol. 2009;70:946–53.CrossRef

23.

Ferrari SM, Materazzi G, Baldini E, Ulisse S, Miccoli P, Antonelli A, et al. Antineoplastic effects of PPARγ agonists, with a special focus on thyroid Cancer. Curr Med Chem. 2016;23:636–49.CrossRefPubMed

24.

Muzza M, Degl’Innocenti D, Colombo C, Perrino M, Ravasi E, Rossi S, et al. The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies. Clin Endocrinol. 2010;72:702–8.CrossRef

25.

Mitsiades CS, Poulaki V, Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer. J Endocrinol. 2003;178:205–16.CrossRefPubMed

26.

Giannini R, Ugolini C, Lupi C, Proietti A, Elisei R, Salvatore G, et al. The heterogeneous distribution of BRAF mutation supports the independent clonal origin of distinct tumor foci in multifocal papillary thyroid carcinoma. J Clin Endocrinol Metab. 2007;92:3511–6.CrossRefPubMed

27.

Antonelli A, Ferrari SM, Fallahi P, Piaggi S, Paolicchi A, Franceschini SS, et al. Cytokines (interferon-γ and tumor necrosis factor-α)-induced nuclear factor-κB activation and chemokine (C-X-C motif) ligand 10 release in graves disease and ophthalmopathy are modulated by pioglitazone. Metabolism. 2011;60:277–83.CrossRefPubMed

28.

Lombardi A, Cantini G, Piscitelli E, Gelmini S, Francalanci M, Mello T, et al. A new mechanism involving ERK contributes to rosiglitazone inhibition of tumor necrosis factor-alpha and interferon-gamma inflammatory effects in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:718–24.CrossRefPubMed

29.

Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127–52.CrossRef

30.

Copland JA, Marlow LA, Kurakata S, Fujiwara K, Wong AK, Kreinest PA, et al. Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene. 2006;25:2304–17.CrossRefPubMed

31.

Sancho M, Vieira JM, Casalou C, Mesquita M, Pereira T, Cavaco BM, et al. Expression and function of the chemokine receptor CCR7 in thyroid carcinomas. J Endocrinol. 2006;19:229–38.CrossRef

32.

Ngo HT, Azab AK, Farag M, Jia X, Melhem MM, Runnels J, et al. Src tyrosine kinase regulates adhesion and chemotaxis in Waldenstrom macroglobulinemia. Clin Cancer Res. 2009;15:6035–41.CrossRefPubMedPubMedCentral

33.

Antonelli A, Bocci G, Fallahi P, La Motta C, Ferrari SM, Mancusi C, et al. CLM3, a multitarget tyrosine kinase inhibitor with antiangiogenic properties, is active against primary anaplastic thyroid cancer in vitro and in vivo. J Clin Endocrinol Metab. 2014;99:E572–81.CrossRefPubMed

34.

Barton BE, Karras JG, Murphy TF, Barton A, Huang HF. Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: direct STAT3 inhibition induces apoptosis in prostate cancer lines. Mol Cancer Ther. 2004;3:11–20.CrossRefPubMed

35.

Xu Z, Choudhary S, Voznesensky O, Mehrotra M, Woodard M, Hansen M, et al. Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis. Cancer Res. 2006;66:6657–64.CrossRefPubMed

36.

Galimberti S, Canestraro M, Pacini S, Fazzi R, Orciuolo E, Trombi L, et al. PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells. Leuk Res. 2008;32:103–12.CrossRefPubMed

37.

Antonelli A, Fallahi P, Delle Sedie A, Ferrari SM, Maccheroni M, Bombardieri S, et al. High values of Th1 (CXCL10) and Th2 (CCL2) chemokines in patients with psoriatic arthtritis. Clin Exp Rheumatol. 2009;27:22–7.PubMed

38.

Antonelli A, Ferri C, Fallahi P, Ferrari SM, Frascerra S, Sebastiani M, et al. High values of CXCL10 serum levels in patients with hepatitis C associated mixed cryoglobulinemia in presence or absence of autoimmune thyroiditis. Cytokine. 2008;42:137–43.CrossRefPubMed

39.

Schweppe RE, Klopper JP, Korch C, Pugazhenthi U, Benezra M, Knauf JA, et al. Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification. J Clin Endocrinol Metab. 2008;93:4331–41.CrossRefPubMedPubMedCentral

40.

Marx N, Mach F, Sauty A, Leung JH, Sarafi MN, Ransohoff RM, et al. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol. 2000;164:6503–8.CrossRefPubMedPubMedCentral

41.

Gosset P, Charbonnier AS, Delerive P, Fontaine J, Staels B, Pestel J, et al. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. Eur J Immunol. 2001;31:2857–65.CrossRefPubMed

42.

Schaefer KL, Denevich S, Ma C, Cooley SR, Nakajima A, Wada K, et al. Intestinal antiinflammatory effects of thiazolidenedione peroxisome proliferator-activated receptor-gamma ligands on T helper type 1 chemokine regulation include nontranscriptional control mechanisms. Inflamm Bowel Dis. 2005;11:244–52.CrossRefPubMed

43.

Yang XY, Wang LH, Farrar WL. A role for PPARgamma in the regulation of cytokines in immune cells and Cancer. PPAR Res. 2008;2008:961753 (Retracted Article; Citation for this retraction: PPAR Res 2015;2015:982750).PubMedPubMedCentral

44.

Ferrari SM, Fallahi P, Vita R, Antonelli A, Benvenga S. Peroxisome proliferator-activated receptor- γ in thyroid autoimmunity. PPAR Res. 2015;2015:232818.CrossRefPubMedPubMedCentral

45.

Antonelli A, Ferrari SM, Fallahi P, Piaggi S, Di Domenicantonio A, Galleri D, et al. Variable modulation by cytokines and thiazolidinediones of the prototype Th1 chemokine CXCL10 in anaplastic thyroid cancer. Cytokine. 2012;59:218–22.CrossRefPubMed

46.

Hayashi N, Nakamori S, Hiraoka N, Tsujie M, Xundi X, Takano T, et al. Antitumor effects of peroxisome proliferator activate receptor gamma ligands on anaplastic thyroid carcinoma. Int J Oncol. 2004;24:89–95.PubMed

47.

Klopper JP, Hays WR, Sharma V, Baumbusch MA, Hershman JM, Haugen BR. Retinoid X receptor-gamma and peroxisome proliferator-activated receptor-gamma expression predicts thyroid carcinoma cell response to retinoid and thiazolidinedione treatment. Mol Cancer Ther. 2004;3:1011–20.PubMed

48.

Fröhlich E, Machicao F, Wahl R. Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture. Endocr Relat Cancer. 2005;12:291–303.CrossRefPubMed

49.

Park JW, Zarnegar R, Kanauchi H, Wong MG, Hyun WC, Ginzinger DG, et al. Troglitazone, the peroxisome proliferator-activated receptor-gamma agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines. Thyroid. 2005;15:222–31.CrossRefPubMed

50.

Aiello A, Pandini G, Frasca F, Conte E, Murabito A. Sacco, et al. Peroxisomal proliferator-activated receptor-gamma agonists induce partial reversion of epithelial-mesenchymal transition in anaplastic thyroid cancer cells. Endocrinology. 2006;147:4463–75.CrossRefPubMed

51.

Martelli ML, Iuliano R, Le Pera I, Sama' I, Monaco C, Cammarota S, et al. Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth. J Clin Endocrinol Metab. 2002;87:4728–35.CrossRefPubMed

52.

Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304:411–8.CrossRefPubMed

53.

Moynihan R. European drug agency extends review of safety of pioglitazone. BMJ. 2011;342:d4105.CrossRefPubMed

54.

Wang YQ, Wada A, Ugai S, Tagawa M. Expression of the Mig (CXCL9) gene in murine lung carcinoma cells generated angiogenesis-independent antitumor effects. Oncol Rep. 2003;10:909–13.PubMed

55.

Zhang R, Tian L, Chen LJ, Xiao F, Hou JM, Zhao X, et al. Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Gene Ther. 2006;13:1263–71.CrossRefPubMed

56.

Hensbergen PJ, Wijnands PG, Schreurs MW, Scheper RJ, Willemze R, Tensen CP. The CXCR3 targeting chemokine CXCL11 has potent antitumor activity in vivo involving attraction of CD8+ T lymphocytes but not inhibition of angiogenesis. J Immunother. 2005;28:343–51.CrossRefPubMed

57.

Chu Y, Yang X, Xu W, Wang Y, Guo Q, Xiong S. In situ expression of IFN-gamma-inducible T cell alpha chemoattractant in breast cancer mounts an enhanced specific anti-tumor immunity which leads to tumor regression. Cancer Immunol Immunother. 2007;56:1539–49.CrossRefPubMed

Titel: The paramount role of cytokines and chemokines in papillary thyroid cancer: a review and experimental results
verfasst von: Poupak Fallahi
Silvia Martina Ferrari
Simona Piaggi
Michaela Luconi
Giulia Cantini
Stefania Gelmini
Giusy Elia
Ilaria Ruffilli
Alessandro Antonelli
Publikationsdatum: 08.01.2019
Verlag: Springer US
Erschienen in: Immunologic Research / Ausgabe 6/2018
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-018-9056-x

Neu im Fachgebiet HNO

16.04.2024 | HNO-Chirurgie | Nachrichten

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

The paramount role of cytokines and chemokines in papillary thyroid cancer: a review and experimental results

Abstract

Highlights

Neu im Fachgebiet HNO

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Update HNO

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Highlights

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2018

Review of the “X chromosome-nucleolus nexus” hypothesis of autoimmune diseases with an update explaining disruption of the nucleolus

Intravenous immunoglobulins for rheumatic disorders and thromboembolic events—a case series and review of the literature

Immune reconstitution therapy (IRT) in multiple sclerosis: the rationale

Suspected adverse effects after human papillomavirus vaccination: a temporal relationship

Routinely utilized in-house assays for infliximab, adalimumab and their anti-drug antibody levels

Antibody-initiated beneficial and harmful immune responses

Neu im Fachgebiet HNO

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Update HNO