Skip to main content

Advertisement

SpringerLink
Log in

Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The process of invasion and metastasis is closely related to the prognosis of oral squamous cell carcinoma (OSCC). Matrix metalloproteinases (MMPs) are a group of enzymes characterized by their ability to degrade extracellular matrix proteins and contribute to the tumor invasion and metastasis. Especially MMP-2 and MMP-9 are known to be related to destruction of basement membrane as collagenases. This study focused on protein expression of MMP-2 and MMP-9 and their extracellular matrix degradation activity in OSCCs.

Methods

Freshly frozen samples from 31 OSCC patients were analyzed for the localization and activity of MMP-2 and MMP-9. Serial frozen sections were used by routine hematoxylin and eosin staining, immunohistochemistry for MMP-2 and MMP-9, and film in situ zymography (FIZ) for gelatinolytic activity. We also evaluated the activity of MMP-2 and MMP-9 by zymography using the same samples as frozen sections. The activated form/proform ratio of MMPs in zymography was evaluated using an image scanner.

Results

In MMP-2 the proportion in T3 and T4 clinical stage groups was significantly higher than that in T1 and T2. The proportion in lymph node metastasis cases (N+) was also significantly higher than that in non-lymph node metastasis cases (N−). In contrast to MMP-2, the activated form/proform ratio of MMP-9 was very low, suggesting that MMP-9 is not activated in the matrix degradation of OSCC, although both MMP-2 and MMP-9 protein expression are presented in tumor cells. FIZ revealed MMP in both tumor cells and stromal cells of 70% of the N+ cases and of 47.6% of the N− cases.

Conclusions

These results indicate that two types of proform and activated form matrix metalloproteinases, MMP-2 and MMP-9, are present in human OSCC, and that the activated MMP-2 could be a main enzymatic activity of gelatinolysis in OSCC. Interaction of tumor cells and stromal cells seems to play an important role in the invasion and metastasis of human OSCC. Combination analysis of zymography and FIZ is a usuful method to detect activity and localization of MMPs in human OSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bogusiewicz M, Stryjecka-Zimmer M, Szymanski M, Rechberger T, Golabek W (2003) Activity of matrix metalloproteinases-2 and -9 in advanced laryngeal cancer. Otolaryngol Head Neck Surg 128:132–136

    Google Scholar 

  • Charous SJ, Stricklin GP, Nanney LB, Netterville JL, Burkey BB (1997) Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol 106:271–278

    Google Scholar 

  • Chen PS, Zhai WR, Zhou XM, Zhang JS, Zhang YE, Ling YQ, Gu YH (2001) Effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells. World J Gastroenterol 7:647–651

    Google Scholar 

  • Cho NH, Shim HS, Rha SY, Kang SH, Hong SH, Choi YD, Hong SJ, Cho SH (2003) Increased expression of matrix metalloproteinase 9 correlates with poor prognostic variables in renal cell carcinoma. Eur Urol 44:560–566

    Google Scholar 

  • Di Nezza LA, Misajon A, Zhang J, Jobling T, Quinn MA, Ostor AG, Nie G, Lopata A, Salamonsen LA (2002) Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer 94:1466–1475

    Article  PubMed  Google Scholar 

  • Dumas V, Kanitakis J, Charvat S, Euvrard S, Faure M, Claudy A (1999) Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas. Anticancer Res 19:2929–2938

    Google Scholar 

  • Gerhards S, Jung K, Koenig F, Daniltchenko D, Hauptmann S, Schnorr D, Loening SA (2001) Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma. Urology 57:675–679

    Google Scholar 

  • Gonzalez-Avila G, Iturria C, Vadillo F, Teran L, Selman M, Perez-Tamayo R (1998) 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in different histologic types of lung cancer cells. Pathobiology 66:5–16

    Google Scholar 

  • Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 149:273–282

    Google Scholar 

  • Iijima T, Minami Y, Nakamura N, Onizuka M, Morishita Y, Inadome Y, Noguchi M (2004) MMP-2 activation and stepwise progression of pulmonary adenocarcinoma: analysis of MMP-2 and MMP-9 with gelatin zymography. Pathol Int 54:295–301

    Google Scholar 

  • Katayama A, Bandoh N, Kishibe K, Takahara M, Ogino T, Nonaka S, Harabuchi Y (2004) Expression of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastasis and prognosis. Clin Cancer Res 10:634–640

    Google Scholar 

  • Koshiba T, Hosotani R, Wada M, Miyamoto Y, Fujimoto K, Lee JU, Doi R, Arii S, Imamura M (1998) Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma. Cancer 82:642–650

    Google Scholar 

  • Kumagai S, Kojima S, Imai K, Nakagawa K, Yamamoto E, Kawahara E, Nakanishi I (1994) Immunohistologic distribution of basement membrane in oral squamous cell carcinoma. Head Neck 16:51–57

    Google Scholar 

  • Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A, Takeuchi H, Shirasuna K (1999) Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck 21:627–638

    Google Scholar 

  • Lebeau A, Nerlich AG, Sauer U, Lichtinghagen R, Lohrs U (1999) Tissue distribution of major matrix metalloproteinases and their transcripts in human breast carcinomas. Anticancer Res 19:4257–4264

    Google Scholar 

  • Lengyel E, Gum R, Juarez J, Clayman G, Seiki M, Sato H, Boyd D (1995) Induction of M (r) 92:000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts. Cancer Res 55:963–967

    Google Scholar 

  • Manenti L, Paganoni P, Floriani I, Landoni F, Torri V, Buda A, Taraboletti G, Labianca R, Belotti D, Giavazzi R (2003) Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma. Eur J Cancer 39:1948–1956

    Google Scholar 

  • Myoung H, Kim MJ, Hong SD, Lee JI, Lim CY, Hong SP (2002) Expression of membrane type I-matrix metalloproteinase in oral squamous cell carcinoma. Cancer Lett 185:201–209

    Google Scholar 

  • Poulsom R, Pignatelli M, Stetler-Stevenson WG, Liotta LA, Wright PA, Jeffery RE, Longcroft JM, Rogers L, Stamp GW (1992) Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am J Pathol 141:389–396

    Google Scholar 

  • Sakata K, Shigemasa K, Nagai N, Ohama K (2000) Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. Int J Oncol 17:673–681

    Google Scholar 

  • Stamenkovic I (2003) Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 200:448–464

    Google Scholar 

  • Talvensaari A, Apaja-Sarkkinen M, Hoyhtya M, Westerlund A, Puistola U, Turpeenniemi T (1999) Matrix metalloproteinase 2 immunoreactive protein appears early in cervical epithelial dedifferentiation. Gynecol Oncol 72:306–311

    Google Scholar 

  • Thomas GT, Lewis MP, Speight PM (1999) Matrix metalloproteinases and oral cancer. Oral Oncol 35:227–233

    Google Scholar 

  • Tokumaru Y, Fujii M, Otani Y, Kameyama K, Imanishi Y, Igarashi N, Kanzaki J (2000) Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma: studies of clinical samples and in vitro cell lines co-cultured with fibroblasts. Cancer Lett 150:15–21

    Google Scholar 

  • Waas ET, Lomme RM, DeGroot J, Wobbes T, Hendriks T (2002) Tissue levels of active matrix metalloproteinase-2 and −9 in colorectal cancer. Br J Cancer 86:1876–1883

    Google Scholar 

  • Yoshizaki T, Maruyama Y, Sato H, Furukawa M (2001) Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma. Int J Cancer 95:44–50

    Google Scholar 

  • Zeng ZS, Cohen AM, Guillem JG (1999) Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis. Carcinogenesis 20:749–755

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oral and Maxillofacial Sciences, Graduate School of Medicine, Gifu University, 1-1 Yanagido, 501-1194, Gifu, Japan

    Keizo Kato, Makoto Toida & Toshiyuki Shibata

  2. Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu, Japan

    Akira Hara, Toshiya Kuno, Nami Kitaori, Zhi Huilan & Hideki Mori

Authors
  1. Keizo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshiya Kuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nami Kitaori
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi Huilan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Makoto Toida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Toshiyuki Shibata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keizo Kato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kato, K., Hara, A., Kuno, T. et al. Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity. J Cancer Res Clin Oncol 131, 340–346 (2005). https://doi.org/10.1007/s00432-004-0654-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-004-0654-8

Keywords

Search

Navigation