Skip to main content
Log in

The role of matrix metalloproteinases 2 and 9 during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. The purpose of this study was to characterize the role of MMPs as depicted by the expression of MMP-2 and MMP-9 during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Male Wistar rats were distributed into three groups of 10 animals each and treated with 4-nitroquinoline 1-oxide solution at 50 ppm through their drinking water for 4, 12, and 20 weeks. Ten animals were used as control group. No histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure; however, immunoexpression of MMP-2 was noticed. The same picture occurred to MMP-9, in which positive expression was detected for this immunomarker. MMP-2 and MMP-9 showed positive expression either in pre-neoplastic lesions at 12 weeks following carcinogen exposure or in well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO. Taken together, our results support the belief that MMP-2 and MMP-9 play important role during malignant transformation and conversion of oral mucosa as assessed by immunohistochemistry.

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

Access this article

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Arenas-Huertero FJ, Herrera-Goepfert R, Delgado-Chavez R, Zinser-Sierra JW, De la Garza-Salazar JG, Herrera-Gomez A, Perez-Cardenas E (1999) Matrix metalloproteinases expressed in squamous cell carcinoma of the oral cavity: correlation with clinicopathologic features and neo-adjuvant chemotherapy response. J Exp Clin Cancer Res 18:279–284

    CAS  PubMed  Google Scholar 

  • Badiglian Filho L, Oshima CT, De Oliveira Lima F, De Oliveira Costa H, De Sousa Damião R, Gomes TS, Gonçalves WJ (2009) Canonical and noncanonical Wnt pathway: a comparison among normal ovary, benign ovarian tumor and ovarian cancer. Oncol Rep 21:313–320

    PubMed  Google Scholar 

  • Bindhu OS, Ramadas K, Sebastian P, Pillai MR (2006) High expression levels of nuclear factor kappa B and gelatinases in the tumorigenesis of oral squamous cell carcinoma. Head Neck 28:916–925

    Article  CAS  PubMed  Google Scholar 

  • Chung AW, Radomski A, Alonso-Escolano D, Jurasz P, Stewart MW, Malinski T, Radomski MW (2004) Platelet-leukocyte aggregation induced by PAR agonists: regulation by nitric oxide and matrix metalloproteinases. Br J Pharmacol 143:845–855

    Article  CAS  PubMed  Google Scholar 

  • Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295:2387–2392

    Article  CAS  PubMed  Google Scholar 

  • Deryugina EI, Quigley JP (2010) Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: Contrasting, overlapping and compensatory functions. Biochim Biophys Acta 1803:103–120

    Article  CAS  PubMed  Google Scholar 

  • Dunne AA, Sesterhenn A, Gerisch A, Teymoortash A, Kuropkat C, Werner JA (2003) Expression of MMP-2, -9 and -13 in cell lines and fresh biopsies of squamous cell carcinomas of the upper aerodigestive tract. Anticancer Res 23:2233–2240

    CAS  PubMed  Google Scholar 

  • Hayashi S, Nonoyama T, Miyajima H (1989) Spontaneous nonthymic cell lymphomas in young Wistar rats. Vet Pathol 26:326–332

    Article  CAS  PubMed  Google Scholar 

  • Herzig M, Christofori G (2002) Recent advances in cancer research, mouse models of tumorigenesis. Biochim Biophys Acta 1602:97–113

    CAS  PubMed  Google Scholar 

  • Li H, Bauzon DE, Xu X, Tschesche H, Cao J, Sang QA (1998) Immunological characterization of cell-surface and soluble forms of membrane type I matrix metalloproteinase in human breast cancer cells and in fibroblasts. Mol Carcinog 22:84–89

    Article  CAS  PubMed  Google Scholar 

  • Lukaszewicz-Zajac M, Mroczko B, KozÅ‚owski M, NikliÅ„ski J, LaudaÅ„ski J, Szmitkowski M (2009) Elevated levels of serum metalloproteinase 9 in patients with esophageal squamous cell carcinoma. Pol Arch Med Wewn 119:558–563

    PubMed  Google Scholar 

  • Minicucci EM, da Silva GN, Ribeiro DA, Favero Salvadori DM (2009) No mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. J Mol Histol 40:71–76

    Article  CAS  PubMed  Google Scholar 

  • Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149

    CAS  PubMed  Google Scholar 

  • Ribeiro DA, Fávero Salvadori DM, da Silva RN, Ribeiro Darros B, Alencar Marques ME (2004) Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oral Oncol 40:910–915

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro DA, Salvadori DM, Marques ME (2005) Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. Int J Exp Pathol 86:375–381

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro DA, Kitakawa D, Domingues MA, Cabral LA, Marques ME (2007) Survivin and inducible nitric oxide synthase production during 4NQO-induced rat tongue carcinogenesis: a possible relationship. Exp Mol Pathol 83:131–137

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro DA, Grilli DG, Salvadori DM (2008) Genomic instability in blood cells is able to predict the oral cancer risk: an experimental study in rats. J Mol Histol 39:481–486

    Article  PubMed  Google Scholar 

  • Scheifele C, Reichart PA (2003) Is there a natural limit of the transformation rate of oral leukoplakia? Oral Oncol 39:470–475

    Article  PubMed  Google Scholar 

  • Seftor REB, Seftor EA, Koshikawa N (2001) Cooperative interaction of laminin 5 γ2 chain, matrix metalloproteinase-2, and membrane type-1-matrix metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 61:6322–6327

    CAS  PubMed  Google Scholar 

  • Shah NG, Trivedi TI, Tankshali RA, Goswami JA, Shah JS, Jetly DH, Kobawala TP, Patel KC, Shukla SN, Shah PM, Verma RJ (2007) Molecular alterations in oral carcinogenesis, significant risk predictors in malignant transformation and tumor progression. Int J Biol Markers 22:132–143

    CAS  PubMed  Google Scholar 

  • Shang ZJ, Ethunandan M, Górecki DC, Brennan PA (2008) Aberrant expression of beta-dystroglycan may be due to processing by matrix metalloproteinases-2 and -9 in oral squamous cell carcinoma. Oral Oncol 44:1139–1146

    Article  CAS  PubMed  Google Scholar 

  • Silva RN, Ribeiro DA, Salvadori DM, Marques ME (2007) Placental glutathione S-transferase correlates with cellular proliferation during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. Exp Toxicol Pathol 59:61–68

    Article  CAS  PubMed  Google Scholar 

  • Stetler-Stevenson WG, Yu AE (2001) Proteases in invasion: matrix metalloproteinases. Semin Cancer Biol 11:143–152

    Article  CAS  PubMed  Google Scholar 

  • Tsai CH, Hsieh YS, Yang SF, Chou MY, Chao ChangY (2003) Matrix metalloproteinase 2 and matrix metalloproteinase 9 expression in human oral squamous cell carcinoma and the effect of protein kinase C inhibitors: preliminary. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:710–716

    Article  PubMed  Google Scholar 

  • Vilen ST, Nyberg P, Hukkanen M, Sutinen M, Ylipalosaari M, Bjartell A, Paju A, Haaparanta V, Stenman UH, Sorsa T, Salo T (2008) Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma. Exp Cell Res 314:914–926

    Article  CAS  PubMed  Google Scholar 

  • Xie M, Sun Y, Li Y (2004) Expression of matrix metalloproteinases in supraglottic carcinoma and its clinical implication for estimating lymph node metastases. Laryngoscope 114:2243–2248

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Wang Y, Chen Z, Sternlicht MD, Hidalgo M, Steffensen B (2005) Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. Cancer Res 65:130–136

    Article  CAS  PubMed  Google Scholar 

  • Yorioka CW, Coletta RD, Alves F, Nishimoto IN, Kowalski LP, Graner E (2002) Matrix metalloproteinase-2 and -9 activities correlate with the disease-free survival of oral squamous cell carcinoma patients. Int J Oncol 20:189–194

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) (Grant numbers: 07/01228-4 and 07/08210-3), CNPq and CAPES. DAR is a recipient of the CNPq fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel Araki Ribeiro.

Additional information

Ana Carolina Cuzzuol Fracalossi and Sandra Regina Miranda contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fracalossi, A.C.C., Miranda, S.R., Oshima, C.T.F. et al. The role of matrix metalloproteinases 2 and 9 during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. J Mol Hist 41, 19–25 (2010). https://doi.org/10.1007/s10735-010-9258-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-010-9258-6

Keywords

Navigation