Full Text:   <2782>

CLC number: R76

On-line Access: 

Received: 2002-08-30

Revision Accepted: 2002-12-12

Crosschecked: 0000-00-00

Cited: 12

Clicked: 5840

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE A 2003 Vol.4 No.4 P.491-501


Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

Author(s):  XU Ya-ping, ZHAO Xue-qun, SOMMER, K., MOUBAYED, P.

Affiliation(s):  The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   xuyap@yahoo.com

Key Words:  Head and neck cancer, Matrix metalloproteinase-2, -9 (MMP-2 and MMP-9), Tissue inhibitor-1 of matrix metalloproteinase (TIMP-1), Cell adhesion molecule 44 variant 6 (CD44 v6), HER2/neu, p53

Share this article to: More

XU Ya-ping, ZHAO Xue-qun, SOMMER, K., MOUBAYED, P.. Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis[J]. Journal of Zhejiang University Science A, 2003, 4(4): 491-501.

@article{title="Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis",
author="XU Ya-ping, ZHAO Xue-qun, SOMMER, K., MOUBAYED, P.",
journal="Journal of Zhejiang University Science A",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis
%A XU Ya-ping
%A ZHAO Xue-qun
%A K.
%A P.
%J Journal of Zhejiang University SCIENCE A
%V 4
%N 4
%P 491-501
%@ 1869-1951
%D 2003
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2003.0491

T1 - Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis
A1 - XU Ya-ping
A1 - ZHAO Xue-qun
A1 - K.
A1 - P.
J0 - Journal of Zhejiang University Science A
VL - 4
IS - 4
SP - 491
EP - 501
%@ 1869-1951
Y1 - 2003
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2003.0491

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase-2,-9 (MMP-2, MMP-9), tissue inhibitor-1 of matrix metalloproteinase (TIMP-1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship (P<0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6, HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage (P<0.01). There was also a trend of MMP-2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence (P<0.05). The expression of TIMP-1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratinizing SCC than that in basaloid SCC (P<0.05). These findings suggested that MMP-2 and MMP-9, HER2/neu and MMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Akiyama,T., Sudo, S., Ogawara, H., Toyoshima, T. and Yamamoto, T., 1986. The product of the human c-erbB2 gene: A 185-kilodalton with tyrosine kinase activity. Science, 323: 1644-1646.

[2]Bahar, R., Kunishi, M., Kayada, Y. and Yashigo, K., 1997. CD44 variants 6 (CD44v6) expression as a progression marker benign, premalignant and malignant oral epithelial tissues. Int J Oral Maxillofac, 26: 443-446.

[3]Baybaud-Diogene, H., Tetu, B., Morency, R., Fortin, A. and Monteil, R.A.,1996. P53 overexpression in Head and Neck Squamous Cell Carcinoma: Review of the literature. Orol Oncol, Eur J Cancer, 32B: 143-149.

[4]Brummer, O., Athar, S., Riethdorf, L., Loning, T. and Herbst, H., 1999. Matrix-metalloproteinase 1, 2, and 3 and their tissue inhibitors 1and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch, 435: 566-573.

[5]Chomchai, J.S., Du, W., Sarkar, F.H., Li, Y.W., Jacobs, J.R., Ensley, J.E., Sakr,W. and Yoo,G.H., 1999. Prognostic significance of p53 gene mutations in laryngeal cancer. Laryngoscope, 109: 455-459.

[6]Curran, S. and Murray, G.I., 2000. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur of Cancer, 36: 1621-1630.

[7]Guthert,U., Hofmann, M., Rudy, W., Reber, S., Zoeller, M., Haussmann, I., Matzku,S., Wenzel, A., Ponta, H. and Herrlich, P., 1991. A new variant of glycoprotein CD44 confers metastastic potential to rat carcinoma cells. Cell, 65: 13-24.

[8]Hong, S.D., Hong, S.P., Lee, J.I. and Lim, C.Y., 2000. Expression of matrix metalloproteinase-2, and -9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncology, 36: 207-213.

[9]Liotta, L.A., 1986. Tumor invasion and metastases-role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res., 46: 1-7.

[10]Lupu, R., Cardillo, M., Harris, L., Hijazi, M. and Rosenberg, K., 1987. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science, 235: 177-182.

[11]Merz, H., Malisius, R., Mannweiler, S., Zhou,R., Hartmenn, W., Orscheschek, K., Moubayed, P. and Feller, A.C., 1995. Methods in laboratory investigation immunoMax: a maximized immunohistochemical method for the retrieval and enhancement of hidden antigens. Laboratory Investigation, 73: 149-156.

[12]Miyajima, J., Nakano, R. and Morimatsu, M., 1995. Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization. Ann Oto Rhino Larygol, 104: 678-684.

[13]O-charoentat, P., Modjtahedi, H., Rhys-Evans, P., Court, WJ., Box, G.M. and Eccless, A., 2000. Epidermal growth factor-like ligands differentially upregulate matrix metalloproteinase-9 in head and neck squamous cell carcinoma. Cancer Res., 60:1121-1128.

[14]Ornstein, D.L., Macnab, J. and Cohn, K.H., 1999. Evidence for tumor host cooperation in regulating MMP-2 expression in human colon cancer. Clin Exp Metastasis, 17: 205-212.

[15]Ostwarld, J., Pracht, O., Rhode, E. and Kramp, B., 1997. Are the products of CD44 exons v5 and v6 markers for metastasis of laryngeal carcinomas Laryngorhinootologie, 76:295-299.

[16]Overall, C.M., 1994. Regulation of tissue inhibitor of matrix metalloproteinase expression, Inhibition of matrix metalloproteinases. Ann NY Acad Sci, 732: 51-67.

[17]Parker, S.L., Tong, T., Bolden, S. and Wingo, P.A., 1997. Cancer statistic, CA Cancer. J Clin, 47: 5-27.

[18]Polette, M., Clavel, C., Birembaut, P. and De Clerck,Y.A., 1996. Localization by in situ hybridization of mRNAs encoding stromelysin 3, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 and head and neck carcinoma. Pathol Res Pract, 189: 1052-1057.

[19]Ro, J., EI-Naggar, A., Ro, J.Y., Blick, M., Frye, D., Fraschini, G., Fritsch, H. and Hortobagyi, G., 1989. C-erbB-2 amplification in node-negative human breast cancer. Cancer Res, 49: 6941-6944.

[20]Tan, M., Yao, J. and Yu, D.,1997. Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. Cancer Res, 57: 1199-1205.

[21]Tantaway, A., Louins, L. and Hamza, M.,1999. Expression of c-erbB-2 oncoprotein in cancer of the larynx in relation to invasion of the cartilagenous framework and prognosis. Eur Arch Otorhinolaryngol, 256: 72-77.

[22]Theillet, C., 1993. P53 genes and solid tumors. Bull Cancer, 80: 693-6.

[23]Vermeulen, P.B., Roland, L., Mertens, V., Van Marck, E., De Bruijn, E.A., Van Oosterom, A.T. and Dirix, L.Y., 1996. Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma. Microvasc Res, 51: 164-174.

[24]Weinstein, G.S., Nuamah, I.F. and Tucker, J., 1996. Moutone K: Evaluation of HER2/neu (c-erbB-2) oncogene expression in organ sections of supraglottic squamous cell carcinoma. Ann Oto Rhinol Laryngol, 105: 275-279.

[25]Xia, W., Lau, Y.K., Zhang, H.Z., Lin, A.R., Lin, L., Kiyokawa, N., Clayman, G.L. and Katz, R.L., 1997. Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma. Clin Cancer Res, 3: 3-9.

[26]Yu, Q. and Stamenkovic, I., 1999. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Gene and Development, 13:35-38.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE