Abstract
Loss of E-cadherin triggers peritoneal dissemination, leading to an adverse prognosis for most patients with epithelial ovarian carcinoma (EOC). Because TWIST mainly regulates the epithelial-to-mesenchymal transition and is one of the E-cadherin repressors, we investigated the possibility that TWIST expression affects peritoneal metastasis of EOC using siRNA technique. In the present study, we showed a correlation between TWIST expression and EOC cellular morphology. Furthermore, we demonstrated that the suppression of TWIST expression in EOC cells (HEY) alters the cellular morphology from a fibroblastic and motile phenotype to an epithelial phenotype, and inhibits the adhesion of these cells to mesothelial monolayers. To investigate the mechanism by which down-regulation of TWIST leads to inhibition of adhesion to mesothelial cells (MCs), expression of adhesion molecules (CD29, CD44 and CD54) were observed. Moreover, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. This findings suggests that reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to MCs and invasion of MCs) and may be a potential therapeutic target for the treatment of this carcinoma.
Similar content being viewed by others
References
Pisani P, Parkin DM, Bray F et al (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:870–873
Naora H, Montell DJ (2005) Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer 5:355–366
Kikkawa F, Matsuzawa K, Arii Y et al (2000) Randomized trial of cisplatin and carboplatin versus cisplatin, vinblastine and bleomycin in ovarian cancer. Gynecol Obstet Invest 50:269–274
Conacci-Sorrell M, Zhurinsky J, Ben-Ze’ev A et al (2002) The cadherin–catenin adhesion system in signaling and cancer. J Clin Invest 109:987–991
Takeichi M (1993) Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol 5:806–811
Varner JA, Cheresh DA (1996) Integrins and cancer. Curr Opin Cell Biol 8:724–730
Ruoslahti E (1999) Fibronectin and its integrin receptors in cancer. Adv Cancer Res 76:1–20
Orr FW, Wang HH, Lafrenie RM et al (2000) Interactions between cancer cells and the endothelium in metastasis. J Pathol 190:310–329
Holly SP, Larson MK, Parise LV et al (2000) Multiple roles of integrins in cell motility. Exp Cell Res 261:69–74
Felding-Habermann B (2003) Integrin adhesion receptors in tumor metastasis. Clin Exp Metastasis 20:203–213
Thiery JP (2002) Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454
Thiery JP, Chopin D (1999) Epithelial cell plasticity in development and tumor progression. Cancer Metastasis Rev 18:31–42
Yang J, Mani SA, Donaher JL et al (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939
Kang Y, Massague J (2004) Epithelial–mesenchymal transitions: twist in development and metastasis. Cell 118:277–279
Kajiyama H, Kikkawa F, Maeda O et al (2002) Increased expression of dipeptidyl peptidase IV in human mesothelial cells by malignant ascites from ovarian carcinoma patients. Oncology 63:158–165
Kajiyama H, Kikkawa F, Khin E et al (2003) Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells. Cancer Res 63:2278–2283
Kajiyama H, Kikkawa F, Suzuki T et al (2002) Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res 62:2753–2757
Melchiori A, Mortarini R, Carlone S et al (1995) The alpha 3 beta 1 integrin is involved in melanoma cell migration and invasion. Exp Cell Res 219:233–242
Bartolazzi A, Cerboni C, Nicotra MR et al (1994) Transformation and tumor progression are frequently associated with expression of the alpha 3/beta 1 heterodimer in solid tumors. Int J Cancer 58:488–491
Van Waes C, Surh DM, Chen Z et al (1995) Increase in suprabasilar integrin adhesion molecule expression in human epidermal neoplasms accompanies increased proliferation occurring with immortalization and tumor progression. Cancer Res 55:5434–5444
Tawil NJ, Gowri V, Djoneidi M et al (1996) Integrin alpha3beta1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Int J Cancer 66:703–710
Schumacher D, Schaumburg-Lever G (1996) Ultrastructural localization of alpha-3 integrin subunit in malignant melanoma and adjacent epidermis. J Cutan Pathol 26:321–326
Kishima H, Shimizu K, Tamura K et al (1999) Monoclonal antibody ONS-M21 recognizes integrin alpha3 in gliomas and medulloblastomas. Br J Cancer 79:333–339
Kreidberg JA (2000) Functions of alpha3beta1 integrin. Curr Opin Cell Biol 12:548–553
Tsuji T, Kawada Y, Kai-Murozono M et al (2002) Regulation of melanoma cell migration and invasion by laminin-5 and alpha3beta1 integrin (VLA-3). Clin Exp Metastasis 19:127–134
Fukushima Y, Ohnishi T, Arita N et al (1998) Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells. Int J Cancer 76:63–72
Hosono J, Narita T, Kimura N et al (1998) Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells. J Surg Oncol 67:77–84
Gangopadhyay A, Lazure DA, Thomas P et al (1998) Adhesion of colorectal carcinoma cells to the endothelium is mediated by cytokines from CEA stimulated Kupffer cells. Clin Exp Metastasis 16:703–712
Ziprin P, Ridgway PF, Pfistermuller KL et al (2003) ICAM-1 mediated tumor-mesothelial cell adhesion is modulated by IL-6 and TNF-alpha: a potential mechanism by which surgical trauma increases peritoneal metastases. Cell Commun Adhes 10:141–154
Khashayar L, Dean JA, Theodore O et al (1999) CD44 and β1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells. Am J Pathol 154:1525–1537
Nelson AR, Fingleton B, Rothenberg ML et al (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149
Sier CF, Kubben FJ, Ganesh S et al (1996) Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer 74:413–417
Kuniyasu H, Troncoso P, Johnston D et al (2000) Relative expression of type IV collagenase, E-cadherin, and vascular endothelial growth factor/vascular permeability factor in prostatectomy specimens distinguishes organ-confined from pathologically advanced prostate cancers. Clin Cancer Res 6:2295–2308
Marti HP, McNeil L, Davies M et al (1993) Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells. Biochem J 291:441–446
Marti HP, Lee L, Kashgarian M et al (1994) Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase. Am J Pathol 144:82–94
Pulyaeva H, Bueno J, Polette M et al (1997) MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin Exp Metastasis 15:111–120
Wang H, Keiser JA (2000) Hepatocyte growth factor enhances MMP activity in human endothelial cells. Biochem Biophys Res Commun 272:900–905
Takahashi M, Tsunoda T, Seiki M et al (2002) Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene 21:5861–5867
Brabletz T, Jung A, Dag S et al (1999) Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155:1033–1038
Crawford HC, Fingleton BM, Rudolph-Owen LA et al (1999) The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 18:2883–2891
Crawford HC, Fingleton B, Gustavson MD et al (2001) The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol 21:1370–1383
Mann B, Gelos M, Siedow A et al (1999) Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA 96:1603–1608
Wielenga VJ, Smits R, Korinek V et al (1999) Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol 154:515–523
He TC, Sparks AB, Rago C et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512
Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426
Roose J, Huls G, van Beest M et al (1999) Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science 285:1923–1926
Gradl D, Kuhl M, Wedlich D et al (1999) The Wnt/Wg signal transducer beta-catenin controls fibronectin expression. Mol Cell Biol 19:5576–5587
Vallin J, Thuret R, Giacomello E et al (2001) Cloning and characterization of three Xenopus slug promoters reveal direct regulation by Lef/beta-catenin signaling. J Biol Chem 276:30350–30358
Hlubek F, Jung A, Kotzor N et al (2001) Expression of the invasion factor laminin gamma2 in colorectal carcinomas is regulated by beta-catenin. Cancer Res 61:8089–8093
Polette M, Gilles C, Nawrocki-Raby B et al (2005) Membrane-type 1 matrix metalloproteinase expression is regulated by zonula occludens-1 in human breast cancer cells. Cancer Res 65:7691–7698
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Terauchi, M., Kajiyama, H., Yamashita, M. et al. Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma. Clin Exp Metastasis 24, 329–339 (2007). https://doi.org/10.1007/s10585-007-9070-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10585-007-9070-1