Роль експресії Е-кадгерину в процесі інвазії папілярного раку щитоподібної залози

В. Г. Хоперія; О. С. Ларін; В. В. Васько

doi:10.24026/1818-1384.1(38).2012.80958

Автор(и)

В. Г. Хоперія Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ, Україна
О. С. Ларін Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ, Україна https://orcid.org/0000-0002-5090-5110
В. В. Васько Педіатричний факультет Університету силових структур, Бетезда (США), США

DOI:

https://doi.org/10.24026/1818-1384.1(38).2012.80958

Ключові слова:

thyroid, cancer, E-cadherin, methylation, metastasis

Анотація

To determine whether the mesenchymal feature of invasive cancer cells is maintained in metastatic sites, we examined E-cadherin methylation and E-cadherin expression in 66 papillary thyroid cancer (PTC) samples and in 34 corresponding lymph node metastases (LNM). Hypermethylation of the E-cadherin gene promoter was detected in 39.3% of the PTCs, and loss of E-cadherin expression correlated with lymphocytic infiltration, extrathyroidal invasion and the presence of metastases. Comparing primary PTCs to the corresponding LNM, E-cadherin methylation status was identical in 60% of the cases. Loss of epigenetic silencing in LNMwas associated with a gain of E-cadherin expression. Hypermethylation of the E-cadherin gene promoter was detected in thyroid cancer cell lines with mesenchymal-like morphology. Loss of E-cadherin expression in these cells correlated with high migratory ability. Inhibition of RAS/ERK or PI3K/AKTsignaling decreased the migratory ability of these cells but did not induce E-cadherin expression. In the cells with epithelial-like morphology, treatments with phorbolester or tumor necrosis factor (TNF)-α resulted in translocation of membranous E-cadherin to the cytoplasm and induction of migration. E-cadherin promoter methylation status and E-cadherin expression were not affected by TNF. Together, dynamic changes in E-cadherin methylation occur during metastatic progression in thyroid cancer. Epigenetic mechanisms and TNF-inducible signaling independently contribute to the regulation of E-cadherin expression and localization. These mechanisms may play a role in the induction of EMTin primary tumors and in the conversion from the mesenchymal to the epithelial phenotype in metastases.

Біографії авторів

В. Г. Хоперія, Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ

V. Khoperia

О. С. Ларін, Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ

O. Larin

В. В. Васько, Педіатричний факультет Університету силових структур, Бетезда (США)

V. Vasko

Посилання

Puxeddu E., Filetti S. The 2009 American thyroid association guidelines for management of thyroid nodules and differentiated thyroid cancer: progress on the road from consensus- to evidence-based practice // Thyroid. – 2009. – Vol.19. – P. 1145-1147. https://doi.org/10.1089/thy.2009.1601

Shook Dand Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development // Mech. Dev. – 2003. – Vol.120. – P.1351-1383. https://doi.org/10.1016/j.mod.2003.06.005

Thiery J.P. Epithelial-mesenchymal transitions in development and pathologies // Cur. Opin. Cell. Biol. – 2003. – Vol.15. – P. 740-746. https://doi.org/10.1016/j.ceb.2003.10.006

Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator // Science. – 1991. – Vol.251. – P. 1451-1455. https://doi.org/10.1126/science.2006419

Matteucci E., Ridolfi E., Desiderio M.A. Hepatocyte growth factor differently influences Met-E-cadherin phosphorylation and downstream signaling pathway in two models of breast cells // Cell. Mol. Life Sci. – 2006. – Vol.63. – P. 2016-2026. https://doi.org/10.1007/s00018-006-6137-0

Wang H., Radjendirane V., Wary K.K., Chakrabarty S. Transforming growth factor beta regulates cell-cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells // Oncogene. – 2004. – Vol.23. – P. 5558-5561. https://doi.org/10.1038/sj.onc.1207701

Honma N., Genda T., Matsuda Y., Yamagiwa S., Takamura M., Ichida Tand Aoyagi Y. MEK/ERK signaling is a critical mediator for integrin-induced cell scattering in highly metastatic hepatocellular carcinoma cells // Lab. Invest. – 2006. – Vol.86. – P. 687-696. https://doi.org/10.1038/labinvest.3700427

Corn P.G., Smith B.D., Ruckdeschel E.S., Douglas D., Baylin S.B., Herman J.G. E-cadherin expression is silenced by 5' CpG island methylation in acute leukemia // Clin. Cancer. Res. – 2000. – Vol.6. – P. 4243-4248.

Gagnon J., Shaker S., Primeau M., Hurtubise Aand Momparler R.L. Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 expression in human breast carcinoma cells // Anticancer Drugs. – 2003. – Vol.4. – P. 193-202.

Lind G.E., Thorstensen L., Lovig T., Meling G.I., Hamelin R., Rognum T.O., Esteller Mand / Lothe R.A. ACpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines // Mol. Cancer. – 2004. – Vol.3. – P. 28. https://doi.org/10.1186/1476-4598-3-28

Jaggi M., Rao P.S., Smith D.J., Wheelock M.J., Johnson K.R., Hemstreet G.P., Balaji K.C. E-cadherin phosphorylation by protein kinase D1/protein kinase C{mu} is associated with altered cellular aggregation and motility in prostate cancer // Cancer Res. – 2005. – Vol.65. – P. 483-492.

Le T.L., Joseph S.R., Yap A.S., Stow J.L. Protein kinase C regulates endocytosis and recycling of E-cadherin // Am. J. Physiol. Cell. Physiol. – 2002. – Vol.283. – P. 489-499. https://doi.org/10.1152/ajpcell.00566.2001

Takahashi E., Nagano O., Ishimoto T., Yae T., Suzuki Y., Shinoda T., Nakamura S., Niwa S., Ikeda S., Koga H., Tanihara Hand Saya H. TNF-{alpha} regulates TGF-{beta}-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-Moesin interaction // J. Biol. Chem. – 2010. – Vol.285. – P. 4060-4073. https://doi.org/10.1074/jbc.m109.056523

Fluge O., Bruland O., Akslen L.A., Lillehaug J. Rand Varhaug J.E. Gene expression in poorly differentiated papillary thyroid carcinomas // Thyroid. – 2006. – Vol.16. – P. 161-175. https://doi.org/10.1089/thy.2006.16.161

Choi Y.L., Kim M.K., Suh J.W., Han J., Kim J.H., Yang J. Hand Nam S.J.: Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas // J. Korean. Med. Sci. – 2005. – Vol.20. – P. 853-859. https://doi.org/10.3346/jkms.2005.20.5.853

Graff J.R., Greenberg V.E., Herman J.G., Westra W.H., Boghaert E.R., Ain K.B., Saji M., Zeiger M.A., Zimmer S.G., Baylin S.B. Distinct patterns of E-cadherin CpG island methylation in papillary, follicular, Hurthle's cell, and poorly differentiated human thyroid carcinoma // Cancer Res. – 1998. – Vol.58. – P. 2063-2066.

Hoque M.O., Rosenbaum E., Westra W.H., Xing M., Ladenson P., Zeiger M.A., Sidransky Dand Umbricht C.B. Quantitative assessment of promoter methylation profiles in thyroid neoplasms // J. Clin. Endocrinol. Metab. – 2005. – Vol.90. – P. 4011-4018. https://doi.org/10.1210/jc.2005-0313

Vasko V., Espinosa A.V., Scouten W., He H., Auer H., Liyanarachchi S., Larin A., Savchenko V., Francis G.L., de la Chapelle A,. Saji M. and Ringel M.D. Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion // Proc. Natl. Acad. Sci. USA. – 2007. – Vol.104. – P. 2803-2808. https://doi.org/10.1073/pnas.0610733104

Brecelj E., Frkovic Grazio S., Auersperg M., Bracko M. Prognostic value of E-cadherin expression in thyroid follicular carcinoma // Eur. J. Surg. Oncol. – 2005. – Vol.31. p- P. 544-548. https://doi.org/10.1016/j.ejso.2005.02.003

Rocha A.S., Soares P., Fonseca E., Cameselle-Teijeiro J., Oliveira M. Cand Sobrinho-Simoes M. E-cadherin loss rather than beta-catenin alterations is a common feature of poorly differentiated thyroid carcinomas // Histopathology. – 2003. – Vol.42. – P. 580-587. https://doi.org/10.1046/j.1365-2559.2003.01642.x

Graff J.R., Gabrielson E., Fujii H., Baylin S.B., Herman J.G. Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression // J. Biol. Chem. – 2000. – Vol.275. – P. 2727-2732. https://doi.org/10.1074/jbc.275.4.2727

Gupta A., Deshpande C.G., Badve S. Role of E-cadherins in development of lymphatic tumor emboli // Cancer. – 2003. – Vol.97. – P. 2341-2347. https://doi.org/10.1002/cncr.11332

Batistatou A., Charalabopoulos A.K., Scopa C.D., Nakanishi Y., Kappas A., Hirohashi S., Agnantis N.J., Charalabopoulos K. Expression patterns of dysadherin and E-cadherin in lymph node metastases of colorectal carcinoma // Virchows Arch. – 2006. – Vol.448. – P. 763-767. https://doi.org/10.1007/s00428-006-0183-8

Friedl P., Noble P.B., Walton P.A., Laird D.W., Chauvin P.J., Tabah R.J., Black Mand Zanker K.S. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro // Cancer Res. – 1995. – Vol.55. – P. 4557-4560.

Nabeshima K., Moriyama T., Asada Y., Komada N., Inoue T., Kataoka H., Sumiyoshi Aand Koono M. Ultrastructural study of TPA-induced cell motility: human well-differentiated rectal adenocarcinoma cells move as coherent sheets via localized modulation of cell-cell adhesion // Clin. Exp. Metastasis. – 1995. – Vol.13. – P. 499-508. https://doi.org/10.1007/bf00118189

Brandt B., Junker R., Griwatz C., Heidl S., Brinkmann O., Semjonow A., Assmann G., Zanker K.S. Isolation of prostate-derived single cells and cell clusters from human peripheral blood // Cancer Res. – 1996. – Vol.56. – P. 4556-4561.