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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

Oncostatin M stimulates cell migration and proliferation by down-regulating E-cadherin in HTR8/SVneo cell line through STAT3 activation

Authors: Hyun Sun Ko, Sae Kyung Choi, Hee Kyung Kang, Ho Shik Kim, Ji Hyun Jeon, In Yang Park, Jong Chul Shin

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

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Abstract

Background

During the first trimester of pregnancy, trophoblastic E-cadherin expression is down-regulated, thereby allowing extravillous trophoblasts (EVTs) to acquire the potential for migration and invasiveness. The aim of the present study was to investigate the role of OSM on the migration and proliferation of EVT cell line HTR8/SVneo with regard to its effects on the expression of E-cadherin and STAT3 activation.

Methods

We investigated the effects of OSM on RNA and protein expression of E-cadherin by real time RT-PCR analyses, western blotting, and indirect immunofluorescence staining in HTR8/SVneo cells, as well as the effects on cell migration and proliferation. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, and STAT3 siRNA were used to investigate STAT3 activation by OSM.

Results

OSM significantly reduced RNA and protein expression of E-cadherin. Indirect immunofluorescence staining of HTR8/SVneo cells also revealed the down-regulation of E-cadherin, compared with the controls. OSM-stimulated cell migration was attenuated by anti-gp130 antibodies. OSM-induced STAT3 phosphorylation, and the down-regulation of E-cadherin by OSM treatment was restored by stattic and STAT3 siRNA. In addition, OSM-stimulated migration and proliferation were significantly suppressed by STAT3 inhibition.

Conclusions

This study suggests that OSM stimulates the migration and proliferation of EVTs during the first trimester of pregnancy through the down-regulation of E-cadherin. In addition, this study suggests that the effects of OSM on migration and proliferation are related to STAT3 activation, which is important in trophoblast invasiveness.
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Literature
1.
Loke YW, King A: Human trophoblast development. Human implantation: cell biology and immunology. 1995, Cambridge: Cambridge University Press, 32-62.
2.
Kaufmann P, Scheffen I: Placental development. Fetal and neonatal physiology. Edited by: Polin RA, Fox WW. 1992, Philadelphia: W.B. Saunders, 47-56.
3.
Vicovac L, Aplin JD: Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat (Basel). 1996, 156: 202-216. 10.1159/000147847.CrossRef
4.
Floridon C, Nielsen O, Holund B, Sunde L, Westergaard JG, Thomsen SG, Teisner B: Localization of E-cadherin in villous, extravillous and vascular trophoblasts during intrauterine, ectopic and molar pregnancy. Mol Hum Reprod. 2000, 6: 943-950. 10.1093/molehr/6.10.943.CrossRefPubMed
5.
Kokkinos MI, Murthi P, Wafai R, Thompson EW, Newgreen DF: Cadherins in the human placenta–epithelial-mesenchymal transition (EMT) and placental development. Placenta. 2010, 31 (9): 747-755. 10.1016/j.placenta.2010.06.017.CrossRefPubMed
6.
Bamber B, Reife RA, Haugen HS, Clegg CH: Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease. J Mol Med. 1998, 76: 61-69. 10.1007/s109-1998-8105-3.CrossRefPubMed
7.
Ogata I, Shimoya K, Moriyama A, Shiki Y, Matsumura Y, Yamanaka K, Nobunaga T, Tokugawa Y, Kimura T, Koyama M, Azuma C, Murata Y: Oncostatin M is produced during pregnancy by decidual cells and stimulates the release of hCG. al. Mol Hum Reprod. 2000, 6: 750-757. 10.1093/molehr/6.8.750.CrossRefPubMed
8.
Lee G, Kil G, Kwon J, Kim S, Yoo J, Shin J: Oncostatin M as a target biological molecule of preeclampsia. J Obstet Gynaecol Res. 2009, 35 (5): 869-875. 10.1111/j.1447-0756.2009.01114.x.CrossRefPubMed
9.
Ko HS, Kang HK, Kim HS, Choi SK, Park IY, Shin JC: The effects of oncostatin M on trophoblast cells: Influence on matrix metalloproteinases-2 and −9, and invasion activity. Placenta. 2012, 33 (11): 908-913. 10.1016/j.placenta.2012.07.014.CrossRefPubMed
10.
Blechschmidt K, Mylonas I, Mayr D, Schiessl B, Schulze S, Becker KF, Jeschke U: Expression of E-cadherin and its repressor snail in placental tissue of normal, preeclamptic and HELLP pregnancies. Virchows Arch. 2007, 450 (2): 195-202. 10.1007/s00428-006-0343-x.CrossRefPubMed
11.
Graham CH, Hawley TS, Hawley RG, MacDougall JR, Kerbel RS, Khoo N, Lala PK: Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res. 1993, 206: 204-211. 10.1006/excr.1993.1139.CrossRefPubMed
12.
Irving JA, Lysiak JJ, Graham CH, Hearn S, Han VK, Lala PK: Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture. Placenta. 1995, 16: 413-433. 10.1016/0143-4004(95)90100-0.CrossRefPubMed
13.
Kilburn BA, Wang J, Duniec-Dmuchowski ZM, Leach RE, Romero R, Armant DR: Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line. Biol Reprod. 2000, 62: 739-747. 10.1095/biolreprod62.3.739.CrossRefPubMed
14.
Ji YQ, Zhang YQ, Li MQ, Du MR, Wei WW, Li da J: EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT-5 and inactivating p38 signal in human early pregnancy. Int J Clin Exp Pathol. 2011, 4 (8): 765-774.PubMedCentralPubMed
15.
Poehlmann TG, Fitzgerald JS, Meissner A, Wengenmayer T, Schleussner E, Friedrich K, Markert UR: Trophoblast invasion: tuning through LIF, signalling via Stat3. Placenta. 2005, 26 (Suppl A): S37-S41.CrossRefPubMed
16.
Jones JI, Gockerman A, Busby WH, Wright G, Clemmons DR: Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. Proc Natl Acad Sci U S A. 1993, 90: 10537-10553.
17.
Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW, Waltham M: Vimentin and epithelial-mesenchymal transition in human breast cancer-observations in vitro and in vivo. Cells Tissues Organs. 2007, 185: 191-203. 10.1159/000101320.CrossRefPubMed
18.
Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 2007, 213: 374-383. 10.1002/jcp.21223.CrossRefPubMed
19.
Argast GM, Mercado P, Mulford IJ, O’Connor M, Keane DM, Shaaban S, Epstein DM, Pachter JA, Kan JL: Cooperative signaling between oncostatin M, hepatocyte growth factor and transforming growth factor-β enhances epithelial to mesenchymal transition in lung and pancreatic tumor models. Cells Tissues Organs. 2011, 193 (1–2): 114-132.CrossRefPubMed
20.
West NR, Murray JI, Watson PH: Oncostatin-M promotes phenotypic changes associated with mesenchymal and stem cell-like differentiation in breast cancer. Oncogene. 2013, 15: 1-10. doi: 10.1038/onc.2013.105 [Epub ahead of print]
21.
Pollack V, Sarközi R, Banki Z, Feifel E, Wehn S, Gstraunthaler G, Stoiber H, Mayer G, Montesano R, Strutz F, Schramek H: Oncostatin M-induced effects on EMT in human proximal tubular cells: differential role of ERK signaling. Am J Physiol Renal Physio. 2007, 293 (5): F1714-1726. 10.1152/ajprenal.00130.2007.CrossRef
22.
Nightingale J, Patel S, Suzuki N, Buxton R, Takagi KI, Suzuki J, Sumi Y, Imaizumi A, Mason RM, Zhang Z: Oncostatin M, a cytokine released by activated mononuclear cells, induces epithelial cell-myofibroblast transdifferentiation via Jak/Stat pathway activation. J Am Soc Nephrol. 2004, 15: 21-32. 10.1097/01.ASN.0000102479.92582.43.CrossRefPubMed
23.
Wheelock MJ, Johnson KR: Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol. 2003, 19: 207-235. 10.1146/annurev.cellbio.19.011102.111135.CrossRefPubMed
24.
Zhao HB, Wang C, Li RX, Tang CL, Li MQDu MR, Hou XF, Li DJ: E-cadherin, as a negative regulator of invasive behavior of human trophoblast cells. Is down-regulated by cyclosporine A via epidermal growth factor/extracellular signal-regulated protein kinase signaling pathway. Biol Reprod. 2010, 83: 370-376. 10.1095/biolreprod.110.083402.CrossRefPubMed
25.
Gómez-Lechón MJ: Oncostatin M: signal transduction and biological activity. Life Sci. 1999, 65 (20): 2019-2030. 10.1016/S0024-3205(99)00296-9.CrossRefPubMed
26.
Fitzgerald JS, Poehlmann TG, Schleussner E, Markert UR: Trophoblast invasion: the role of intracellular cytokine signalling via signal transducer and activator of transcription 3 (STAT3). Hum Reprod Update. 2008, 14 (4): 335-344. 10.1093/humupd/dmn010.CrossRefPubMed
27.
Sanseverino I, Purificato C, Gauzzi MC, Gessani S: Revisiting the specificity of small molecule inhibitors: the example of stattic in dendritic cells. Chem Biol. 2012, 19 (10): 1213-1214. 10.1016/j.chembiol.2012.08.021.CrossRefPubMed
28.
Chaddha V, Viero S, Huppertz B, Kingdom J: Developmental biology of the placenta and the origins of placental insufficiency. Semin Fetal Neonatal Med. 2004, 9: 357-369. 10.1016/j.siny.2004.03.006.CrossRefPubMed
29.
Kaufmann P, Black S, Huppertz B: Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003, 69: 1-7. 10.1095/biolreprod.102.014977.CrossRefPubMed
30.
Aplin JD, Jones CJP, Harria LK: Adhesion molecules in human trophoblast - a review. I. Villous trophoblast. Placenta. 2009, 30: 293-298. 10.1016/j.placenta.2008.12.001.CrossRefPubMed
31.
Chen Q, Stone P, Ching LM, Chamley L: A role for interleukin-6 in spreading endothelial cell activation after phagocytosis of necrotic trophoblastic material: implications for the pathogenesis of pre-eclampsia. J Pathol. 2009, 217 (1): 122-130. 10.1002/path.2425.CrossRefPubMed
32.
Jovanović M, Vićovac L: Interleukin-6 stimulates cell migration, invasion and integrin expression in HTR8/SVneo cell line. Placenta. 2009, 30 (4): 320-328. 10.1016/j.placenta.2009.01.013.CrossRefPubMed
33.
Champion H, Innes BA, Robson SC, Lash GE, Bulmer JN: Effects of interleukin-6 on extravillous trophoblast invasion in early human pregnancy. Mol Hum Reprod. 2012, 18 (8): 391-400. 10.1093/molehr/gas010.CrossRefPubMed
34.
Suman P, Shembekar N, Gupta SK: Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of matrix metalloproteinases. Fertil Steril. 2013, 99 (2): 533-542. 10.1016/j.fertnstert.2012.10.004.CrossRefPubMed
Metadata
Title
Oncostatin M stimulates cell migration and proliferation by down-regulating E-cadherin in HTR8/SVneo cell line through STAT3 activation
Authors
Hyun Sun Ko
Sae Kyung Choi
Hee Kyung Kang
Ho Shik Kim
Ji Hyun Jeon
In Yang Park
Jong Chul Shin
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-93

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