Abstract
Ovarian cancer is the third most common gynecologic malignancy and the leading cause of death in gynecological cancer. Although the 5-year survival rate is increasing, peritoneal metastasis of ovarian cancer is still a problem because of no potential predictor. Heat shock proteins (HSPs) are a class of functionally related proteins that are highly expressed in many malignant cancers. Previous studies suggest high levels of HSP27 present in the serum of patients with ovarian cancer. In this study, we investigated whether the expression of HSP27 in epithelial ovarian cancer tissue was associated with peritoneal metastasis and whether HSP27 could be used as a potential predictor of peritoneal metastasis in epithelial ovarian cancer. Tissues from epithelial ovarian cancer with or without peritoneal metastasis were collected and the levels of HSP27 messenger RNA and protein determined by real-time polymerase chain reaction and Western blotting. Immunohistochemistry was used to determine the subcellular localization of HSP27. Immunohistochemistry images showed that HSP27 was highly expressed in the cytoplasm of epithelial cancer cells with peritoneal metastasis. Messenger RNA and protein levels of HSP27 were significantly increased in epithelial ovarian cancer with peritoneal metastasis compared with epithelial ovarian cancer without peritoneal metastasis. Higher expression of HSP27 correlated with poor clinical outcome. These data suggest that higher level of HSP27 was associated with peritoneal metastasis in epithelial ovarian cancer. Heat shock protein 27 may be a useful prognostic marker of poor survival and may provide a basis for the development of molecular therapeutics modulating this survival pathway.
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Edwards BK, Brown ML, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975–2002, featuring populationbased trends in cancer treatment. J Nat Cancer Inst. 2005;97(17):1407
McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996;334(l):1–6
Chow SN, Chen RJ, Chen CH, et al. Analysis of protein profiles in human epithelial ovarian cancer tissues by proteomic technology. Eur J Gynaecol Oncol. 2010;31(1):55–62
Cohen M, Dromard M, Petignat P. Heat shock proteins in ovarian cancer: a potential target for therapy. Gynecol oncol. 2010;119(1):164–166
De Maio A. Heat shock proteins: facts, thoughts, and dreams. Shock. 1999;11(1):1
Mattila K, Valtonen V, Nieminen MS, Asikainen S. Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. Clin infect dis. 1998;26(3):719
Tang D, Khaleque MA, Jones EL, et al. Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones. 2005;10(1):46
Elpek GÖ, Karaveli IM, Ek T, Kele N, Aksoy NH. Expression of heat shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. APMIS. 2003;111(4):523–530
Arts HJG, Hollema H, Lemstra W, et al. Heat shock protein 27 (HSP27) expression in ovarian carcinoma: relation in response to chemotherapy and prognosis. Int J cancer. 1999;84(3):234–238
Sarto C, Binz PA, Mocarelli P. Heat shock proteins in human cancer. Electrophoresis. 2000;21(6):1218–1226
Olejek A, Damasiewicz-Bodzek A, Bodzek P, et al. Concentrations of antibodies against heat shock protein 27 in the sera of women with ovarian carcinoma. Int J Gynecol Cancer. 2009;19(9):1516
Rui Z, Jian Guo J, Yuan Peng T, Hai P, Bing Gen R. Use of serological proteomic methods to find biomarkers associated with breast cancer. Proteomics. 2003;3(4):433–439
Vargas-Roig LM, Fanelli MA, Lopez LA, et al. Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prev. 1997;21(5):441
Alaiya AA, Franzen B, Moberger B, Silfverswärd C, Linder S, Auer G. Two dimensional gel analysis of protein expression in ovarian tumors shows a low degree of intratumoral heterogeneity. Electrophoresis. 1999;20(4–5):1039–1046
Jiang D, Ying W, Lu Y, et al. Identification of metastasis associated proteins by proteomic analysis and functional exploration of interleukin 18 in metastasis. Proteomics. 2003;3(5):724–737
Kim J, Kim SH, Lee SU, et al. Proteome analysis of human liver tumor tissue by two dimensional gel electrophoresis and matrixassisted laser desorption/ionization mass spectrometry for identification of disease related proteins. Electrophoresis. 2002;23(24):4142–4156
Adams DJ, Hajj H, Edwards DP, Bjercke RJ, McGuire WL. Detection of a Mr 24,000 estrogen-regulated protein in human breast cancer by monoclonal antibodies. Cancer res. 1983;43(9):4297
Tenniswood MP, Guenette RS, Lakins J, Mooibroek M, Wong P, Welsh JE. Active cell death in hormone-dependent tissues. Cancer Metastasis Rev. 1992;11(2):197–220
Love S, King R. A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer. Br J cancer. 1994;69(4):743
Foster C, Dodson A, Ambroisine L, et al. Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement. Br J cancer. 2009;101(7):1137–1144
Morino M, Tsuzuki T, Ishikawa Y, et al. Specific regulation of HSPs in human tumor cell lines by flavonoids. In Vivo. 1997;11(3):265
Lemieux P, Oesterreich S, Lawrence J, et al. The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells. Invasion Metastasis. 1997;17(3):113
Oesterreich S, Weng CN, Qiu M, Hilsenbeck SG, Osborne CK, Fuqua SAW. The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res. 1993;53(19):4443
Annunziata CM, Kleinberg L, Davidson B, et al. BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer. Clin Cancer Res. 2007;13(22):6585
Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10(2):86
Melle C, Ernst G, Escher N, et al. Protein profiling of microdissected pancreas carcinoma and identification of HSP27 as a potential serum marker. Clin chem. 2007;53(4):629
Beere HM. Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Investigation. 2005;115(10):2633
Elstrand MB, Kleinberg L, Kohn EC, Trope CG, Davidson B. Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. Int J Gynecol Pathol. 2009;28(3):211–221
Fujiwara K, Shirafuji H, Fushitani K, Fujimoto K, Kohno I, Modest E. Change in the localization of heat shock protein 27 (HSP 27) in BG-1 human ovarian cancer cells following treatment by the ether lipid ET-18-OCH3. Anticancer Res. 1999;19(1A):181–187
Marin R, Tanguay R. Stage-specific localization of the small heat shock protein Hsp27 during oogenesis inDrosophila melanogaster. Chromosoma. 1996;105(3):142–149
Robitaille H, Simard-Bisson C, Larouche D, Tanguay RM, Blouin R, Germain L. The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression. J Invest Dermatol. 2009;130(l):74–85
Jiang Y, Woronicz JD, Liu W, Goeddel DV. Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science. 1999;283(5401):543
Miki K, Eddy EM. Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain. Mol Cell Biol. 2002;22(8):2536
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Zhao, M., Shen, F., Yin, Y.X. et al. Increased Expression of Heat Shock Protein 27 Correlates With Peritoneal Metastasis in Epithelial Ovarian Cancer. Reprod. Sci. 19, 748–753 (2012). https://doi.org/10.1177/1933719111432875
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DOI: https://doi.org/10.1177/1933719111432875