STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Purpose: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanismsassociated with these events in the immortalized human trophoblast cell line HTR8/SVneo. Materials and Methods: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasionactivity were further determined via Western blot and gelatin zymography. Results: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increasedinvasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extentby STAT3 inhibition. Conclusion: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activationof STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.
Abstract
Purpose: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanismsassociated with these events in the immortalized human trophoblast cell line HTR8/SVneo. Materials and Methods: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasionactivity were further determined via Western blot and gelatin zymography. Results: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increasedinvasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extentby STAT3 inhibition. Conclusion: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activationof STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.
참고문헌 (25)
- Cohen M, "Metalloproteinases and human placental invasiveness", Placenta, 27, pp.783~793 (2006)
- Ogata I, "Oncostatin M is produced during pregnancy by decidual cells and stimulates the release of HCG", Mol Hum Reprod, 6, pp.750~757 (2000)
- Fitzgerald JS, "Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells", Int J Biochem Cell Biol, 37, pp.2284~2296 (2005)
- Ko HS, "The effects of oncostatin M on trophoblast cells: influence on matrix metalloproteinases-2 and -9, and invasion activity", Placenta, 33, pp.908~913 (2012)
- Graham CH, "Establishment and characterization of first trimester human trophoblast cells with extended lifespan", Exp Cell Res, 206, pp.204~211 (1993)
- Irving JA, "Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture", Placenta, 16, pp.413~433 (1995)
- Kilburn BA, "Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line", Biol Reprod, 62, pp.739~747 (2000)
- Busch S, "mTOR mediates human trophoblast invasion through regulation of matrix-remodeling enzymes and is associated with serine phosphorylation of STAT3", Exp Cell Res, 315, pp.1724~1733 (2009)
- Ko HS, "Oncostatin M stimulates cell migration and proliferation by downregulating E-cadherin in HTR8", SVneo cell line through STAT3activation, 2013, pp.11, 93~
- Poehlmann TG, "Trophoblast invasion: tuning through LIF, signalling via Stat3", Placenta, 26(Suppl A), pp.S37~S41 (2005)
- Buettner R, "Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention", Clin Cancer Res, 8, pp.945~954 (2002)
- Suman P, "LIF-STAT signaling and trophoblast biology", JAKSTAT, 2, pp.e25155~ (2013)
- Fitzgerald JS, "Tro-phoblast invasion: the role of intracellular cytokine signalling via signal transducer and activator of transcription 3 (STAT3)", Hum Reprod Update, 14, pp.335~344 (2008)
- Fossey SL, "Oncostatin M promotes STAT3 activation, VEGF production, and invasion in osteosarcoma cell lines", BMC Cancer, 11, pp.125~ (2011)
- Snyder M, "Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration", J Biol Chem, 286, pp.38886~38893 (2011)
- Pijnenborg R, "Implantation and immunology : maternal inflammatory and immune cellular responses to implantation and trophoblast invasion", Reprod Biomed Online, 4(Suppl 3), pp.14~17 (2002)
- Genbacev O, "Regulation of human placental development by oxygen tension", Science, 277, pp.1669~1672 (1997)
- De Marco CS, "Mechanisms of oxygen sensing in human trophoblast cells", 23(Suppl A), pp.S58~S68 (2002)
- Zygmunt M, "Invasion of cytotrophoblastic JEG-3 cells is stimulated by hCG in vitro", Placenta, 19, pp.587~593 (1998)
- Mandl M, "Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models", Histochem Cell Biol, 117, pp.391~399 (2002)
- Liu HY, "Hepatocyte growth factor regulates HLX1 gene expression to modulate HTR-8", SVneo trophoblast cells, 2012, pp.10, 83~
- Cartwright JE, "Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide", Br J Pharmacol, 128, pp.181~189 (1999)
- Lash GE, "The effects of angiogenic growth factors on extravillous trophoblast invasion and motility", Placenta, 20, pp.661~667 (1999)
- Bilban M, "Trophoblast invasion: assessment of cellular models using gene expression signatures", Placenta, 31, pp.989~996 (2010)
- Lash GE, "Effect of low oxygen concentrations on trophoblast-like cell line invasion", Placenta, 28, pp.390~398 (2007)