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Tumor Biology
Published in: Tumor Biology 8/2014

01-08-2014 | Research Article

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma

Authors: Qin Xu, Mingang Ying, Guilin Chen, Ang Lin, Yunqing Xie, Noriyuki Ohara, Dongmei Zhou

Published in: Tumor Biology | Issue 8/2014

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Abstract

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients’ survival rates was assessed by Kaplan–Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.
Literature
1.
Rock CL, Michael CW, Reynolds RK, Ruffin MT. Prevention of cervix cancer. Crit Rev Oncol Hematol. 2000;33:169–85.PubMedCrossRef
2.
Willmott LJ, Monk BJ. Cervical cancer therapy: current, future and anti-angiogensis targeted treatment. Expert Rev Anticancer Ther. 2009;9(7):895–903.PubMedCrossRef
3.
Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997;385:729–33.PubMedCrossRef
4.
Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, et al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α. Nature. 1997;385:733–6.PubMedCrossRef
5.
Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, et al. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol. 2004;164:769–79.PubMedCentralPubMedCrossRef
6.
Gaffney DK, Haslam D, Tsodikov A, Hammond E, Seaman J, Holden J, et al. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2003;56:922–8.PubMedCrossRef
7.
Hambek M, Solbach C, Schnuerch HG, Roller M, Stegmueller M, Sterner-Kock A, et al. Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy. Cancer Res. 2001;61:1045–9.PubMed
8.
Mochizuki S, Okada Y. ADAMs in cancer cell proliferation and progression. Cancer Sci. 2007;98:621–8.PubMedCrossRef
9.
Nakagawa M, Nabeshima K, Asano S, Hamasaki M, Uesugi N, Tani H, et al. Up-regulated expression of ADAM17 in gastrointestinal stromal tumors: coexpression with EGFR and EGFR ligands. Cancer Sci. 2009;100:654–62.PubMedCrossRef
10.
Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H, Röcken C. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol. 2005;131:41–8.PubMedCrossRef
11.
Levano KS, Kenny PA. Clarification of the C-terminal proteolytic processing site of human amphiregulin. FEBS Lett. 2012;586:3500–2.PubMedCrossRef
12.
Higginbotham JN, Beckler MD, Gephart JD, Franklin JL, Bogatcheva G, Kre-mers G-J, et al. Amphiregulin exosomes increase cancer cell invasion. CurrBiol. 2011;21:779–86.CrossRef
13.
Busser B, Sancey L, Brambilla E, Coll J-L, Hurbin A. The multiple roles of amphiregulin in human cancer. Biochim Biophys Acta. 1816;2011:119–31.
14.
Suzuki S, Sato M, Senoo H, Ishikawa K. Direct cell–cell interaction enhances pro-MMP-2 production and activation in co-culture of laryngeal cancer cells and fibroblasts: involvement EMMPRIN MT1-MMP. Exp Cell Res. 2004;293:259–66.PubMedCrossRef
15.
Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 2005;65:3193–9.PubMed
16.
Riethdorf S, Reimers N, Assmann V, Kornfeld JW, Terracciano L, Sauter G, et al. High incidence of EMMPRIN expression in human tumors. Int J Cancer. 2006;119:1800–10.PubMedCrossRef
17.
Tang Y, Kesavan P, Nakada MT, Yan L. Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res. 2004;2:73–80.PubMed
18.
Mi Z, Oliver T, Guo H, Gao C, Kuo PC. Thrombin-cleaved COOH (-) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells. Cancer Res. 2007;67:4088–97.PubMedCrossRef
19.
Gabison EE, Mourah S, Steinfels E, Yan L, Hoang-Xuan T, Watsky MA, et al. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction. Am J Pathol. 2005;166:209–19.PubMedCentralPubMedCrossRef
20.
Zhong WD, Chen QB, Ye YK, Han ZD, Bi XC, Dai QS, et al. CD147, MMP-1, MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer. Oncology. 2008;75:230–6.PubMedCrossRef
21.
Li Y, Shang P, Qian AR, Wang L, Yang Y, Chen ZN. Inhibitory effects of antisense RNA of HAb18G/CD147 on invasion of hepatocellular carcinomacells in vitro. World J Gastroenterol. 2003;9(10):2174–7.PubMed
22.
Zhong WD, Chen QB, Ye YK, Han ZD, Bi XC, Dai QS, et al. Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer. Cancer Epidemiol. 2010;34:478–82.PubMedCrossRef
23.
Piao S, Zhao S, Guo F, Xue J, Yao G, Wei Z, et al. Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol. 2012;138:627–35.PubMedCrossRef
24.
25.
Sheu BC, Lien HC, Ho HN, Lin HH, Chow SN, Huang SC, et al. Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer. Cancer Res. 2003;63:6537–42.PubMed
26.
Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55:434–9.PubMed
27.
Van der Jagt MF, Wobbes T, Strobbe LJ, Sweep FC, Span PN. Metalloproteinases and their regulators in colorectal cancer. J Surg Oncol. 2010;101:259–69.PubMed
28.
Pinheiro C, Longatto-Filho A, Pereira SM, Etlinger D, Moreira MA, Jubé LF, et al. Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma. Dis Markers. 2009;26:97–103.PubMedCentralPubMedCrossRef
29.
Ju XZ, Yang JM, Zhou XY, Li ZT, Wu XH. EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer. Clin Cancer Res. 2008;14:494–501.PubMedCrossRef
30.
Boye K, Nesland JM, Sandstad B, Haugland Haugen M, Mælandsmo GM, et al. EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer. Br J Cancer. 2012;107:667–74.PubMedCentralPubMedCrossRef
31.
Murphy G. The ADAMs: signalling scissors in the tumour micro-environment. Nat Rev Cancer. 2008;8:929–41.PubMedCrossRef
32.
Lin P, Sun X, Feng T, Zou H, Jiang Y, Liu Z, et al. ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Mol Cell Biochem. 2012;359:235–43.PubMedCrossRef
33.
Tanaka Y, Miyamoto S, Suzuki SO, Oki E, Yagi H, Sonoda K, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res. 2005;11:4783–92.PubMedCrossRef
34.
Reddy KB, Krueger JS, Kondapaka SB, Diglio CA. Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int J Cancer. 1999;82:268–73.PubMedCrossRef
35.
Price DJ, Avraham S, Feuerstein J, Fu Y, Avraham HK. The invasive phenotype in HMT-3522 cells requires increased EGF receptor signaling through both PI 3-kinase and ERK 1, 2 pathways. Cell Commun Adhes. 2002;9:87–102.PubMedCrossRef
36.
Xu Q, Ohara N, Liu J, Amano M, Sitruk-Ware R, Yoshida S, et al. Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells. Mol Hum Reprod. 2008;14:181–91.PubMedCrossRef
37.
Yu W, Liu J, Xiong X, Ai Y, Wang H. Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract. 2009;205:709–15.PubMedCrossRef
38.
Li Y, Wu T, Zhang B, Yao Y, Yin G. Matrix metalloproteinase-9 is a prognostic marker for patients with cervical cancer. Med Oncol. 2012;29:3394–9.PubMedCrossRef
39.
Xu P, Derynck R. Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. Mol Cell. 2010;37:551–66.PubMedCrossRef
40.
41.
Sisto M1, Lisi S, D'Amore M, Lofrumento DD. The metalloproteinase ADAM17 and the epidermal growth factor receptor (EGFR) signaling drive the inflammatory epithelial response in Sjögren's syndrome. Clin Exp Med. 2014 Mar 25.
42.
Xiao LJ, Lin P, Lin F, Liu X, Qin W, Zou HF, et al. ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. Int J Oncol. 2012;40:1714–24.PubMed
43.
Jin JS, Wu CY, Lin YF, Wang JY, Yu CP, Sheu LF, et al. Higher expression of epidermal growth factor receptor is associated with extracellular matrixmetalloprotease inducer in colorectal adenocarcinoma: tissue microarray analysis of immunostaining score with clinicopathological parameters. Dis Markers. 2006;22:309–16.PubMedCentralPubMedCrossRef
44.
Menashi S, Serova M, Ma L, Vignot S, Mourah S, Calvo F. Regulation of extracellular matrix metalloproteinase inducer and matrix metalloproteinase expression by amphiregulin in transformed human breast epithelial cells. Cancer Res. 2003;63:7575–80.PubMed
Metadata
Title
ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma
Authors
Qin Xu
Mingang Ying
Guilin Chen
Ang Lin
Yunqing Xie
Noriyuki Ohara
Dongmei Zhou
Publication date
01-08-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 8/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1990-1

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