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Serum Levels of MMP9 and MMP2 in Patients with Oral Squamous Cell Carcinoma

  • Lotfi, Alireza (Department of Otorhinolaryngology, Tabriz University of Medical Sciences) ;
  • Mohammadi, Ghodrat (Department of Otorhinolaryngology, Tabriz University of Medical Sciences) ;
  • Tavassoli, Atena (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • mousaviagdas, Mehrnoosh (Department of Otorhinolaryngology, Tabriz University of Medical Sciences) ;
  • Chavoshi, Hadi (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • Saniee, Lale (Hematology and Oncology Research Center, Tabriz University of Medical Sciences)
  • Published : 2015.03.09

Abstract

Background: Squamous cell carcinoma (SCC) is the most common cancer in the oral area. Matrix metalloproteinases (MMPs) and especially MMP-2 and MMP-9 are increased in malignancy and lymph node involvement in oral SCCs. We aimed to evaluate the serum levels of MMP-2 and MMP-9 in patients with oral SCC compared to normal subjects and their relation with clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included and serum levels of MMP-2 and MMP-9 were compared between groups. Also, the correlation between these markers with clinicopathological findings including grade (T) and node (N) were evaluated. Results: Patients with oral SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p<0.001) compared to healthy subjects. With increase in grade T, MMP-2 was significantly increased (p=0.001), but in the MMP-9 case this was not significant (p=0.27). The levels of MMP-2 (p=0.002) and MMP-9 (p=0.01) in cases with lymph node involvement and that of MMP-2 in subjects with smoking history (p=0.001) were significantly high. There was significantly positive correlation between MMP-2 with grade T tumor (r=0.598, p=0.005), lymph node involvement (r=0.737, p<0.001) and smoking (r=0.674, p=0.001) and also between MMP-9 and lymph node involvement (r=0.474, p=0.03). Conclusions: Both markers are significantly increased in oral SCC compared to healthy subjects. However, MMP-2 was better for evaluating lymph node involvement and tumor grade.

Keywords

Squamous cell carcinoma;matrix metalloproteinase 2;matrix metalloproteinase 9;grade

Acknowledgement

Grant : which was a part of Otorhinolaryngology sub-specialty thesis no. 92/3-5/5

Supported by : Tabriz University of Medical Sciences

References

  1. Abbasi MM, Jahanban-Esfahlan R, Monfaredan A, et al (2014). Oral and IV dosages of doxorubicin-methotrexate loadednanoparticles inhibit progression of oral cancer by downregulation of matrix methaloproteinase 2 expression in vivo. Asian Pac J Cancer Prev, 15, 10705-11.
  2. Bedal KB, Grassel S, Oefner PJ, et al (2014). Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma. PLoS ONE, 9, 86777. https://doi.org/10.1371/journal.pone.0086777
  3. Di Domenico M, Ricciardi C, Fusco A, Pierantoni GM (2011). Anti-VEGF therapy in breast and lung mouse models of cancers. J Biomed Biotechnol, 2011, 947928.
  4. de Vicente JC, Fresno MF, Villalain L, et al (2005). Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma. Oral Oncol, 41, 283-93. https://doi.org/10.1016/j.oraloncology.2004.08.013
  5. Elahi M, Rakhshan V, Ghasemian NT, Moshref M (2012). Prognostic value of transforming growth factor beta 1 [TGF-${\beta}1$] and matrix metalloproteinase 9 [MMP-9] in oral squamous cell carcinoma. Biomarkers, 17, 21-7. https://doi.org/10.3109/1354750X.2011.635804
  6. Erdem NF, Carlson ER, Gerard DA, Ichiki AT (2007). Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials. J Oral Maxillofac Surg, 65, 1725-33. https://doi.org/10.1016/j.joms.2006.11.034
  7. Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C (2004). Matrix metalloproteinases in cancer: from new functions to improved inhabitation strategies. Int J Dev Biol, 48, 411-24. https://doi.org/10.1387/ijdb.041811af
  8. Forsyth PA, Wong H, Laing TD, et al (1999). Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer, 79, 1828-35. https://doi.org/10.1038/sj.bjc.6990291
  9. Garvin P, Nilsson L, Carstensen J, Jonasson L, Kristenson M (2008). Circulating matrix metalloproteinase-9 is associated with cardiovascular risk factors in a middle-aged normal population. PLoS One, 3, 1774. https://doi.org/10.1371/journal.pone.0001774
  10. Hong Q, Jun T, Lei J, Xiling J, Tamamura R (2006). Expression and clinical significance of matrix metalloproteinase-2 and its inhibitor TIMP-2 in oral squamous cell carcinoma. J Hard Tissue Biol, 15, 54-60. https://doi.org/10.2485/jhtb.15.54
  11. Johnson NW, Jayasekara P, Amarasinghe AA (2011). Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology. Periodontology, 57, 19-37. https://doi.org/10.1111/j.1600-0757.2011.00401.x
  12. Katayama A, Bandoh N, Kishibe K, et al (2004). Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res, 10, 634-40. https://doi.org/10.1158/1078-0432.CCR-0864-02
  13. Knapinska A, Fields GB (2012). Chemical biology for understanding matrix metalloproteinase function. Chembiochem, 13, 2002-20. https://doi.org/10.1002/cbic.201200298
  14. Kondakova IV, Klisho EV, savenkova OV (2008). Matrix metalloproteinase 2 and 9 as the factor of head and neck tumor metastasis. Biomed Khim, 54, 555-60.
  15. Li M, Wang Z, Xing Y, et al (2014). A Multicenter study on expressions of vascular endothelial growth factor, matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-2 in oral and maxillofacial squamous cell carcinoma. Iran Red Crescent Med J, 16, 13185.
  16. Liu G, Li J, Li Z, Chen X (2001). The effects of MMPs and TIMPs on the metastasis of oral squamous cell carcinoma to neck lymph nodes. Hua Xi Kou Qiang Yi Xue Za Zhi, 19, 216-8, 224 (in Chinese).
  17. Makinen LK, Hayry V, Atula T, et al (2012). Prognostic significance of matrix metalloproteinase-2, -8, -9, and -13 in oral tongue cancer. J Oral Pathol Med, 41, 394-9. https://doi.org/10.1111/j.1600-0714.2011.01110.x
  18. Mardani M, Andisheh-Tadbir A, Khademi B, Biparva P, Malekzadeh M (2014). Serum level of matrix metalloproteinase-9 in patients with salivary gland tumor. J Dent Shiraz Univ Med Sci, 15, 199-203.
  19. Mohtasham N, Babakoohi S, Shiva A, et al (2013). Immunohistochemical study of p53, Ki-67, MMP-2 and MMP-9 expression at invasive front of squamous cell and verrucous carcinoma in oral cavity. Pathol Res Pract, 209, 110-4. https://doi.org/10.1016/j.prp.2012.11.002
  20. Monteiro-Amado F, Castro-Silva II, Lima CJ, et al (2013). Immunohistochemical evaluation of MMP-2, MMP-9 and CD31/microvascular density in squamous cell carcinomas of the floor of the mouth. Braz Dent J, 24, 3-9. https://doi.org/10.1590/0103-6440201301941
  21. Nikkola J, Vihinen P, Vuoristo MS, et al (2005). High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma. Clin Cancer Res, 11, 5158-66. https://doi.org/10.1158/1078-0432.CCR-04-2478
  22. Pereira AC, Dias do Carmo E, Dias da Silva MA, Blumer Rosa LE (2012). Matrix metalloproteinase gene polymorphisms and oral cancer. J Clin Exp Dent, 4, 297-301.
  23. Rosenthal EL, Matrisian LM (2006). Matrix metalloproteinases in head and neck cancers. Head Neck, 10, 639-48.
  24. SahebJamee M, Eslami M, AtarbashiMoghadam F, Sarafnejad A (2008). Salivary concentration of INF6, TNFa, IL1a, and IL8 in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal, 13, 292-5.
  25. Singh RD, Haridas N, Patel JB, et al (2010). Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. Indian J Clin Biochem, 25, 250-9. https://doi.org/10.1007/s12291-010-0060-8
  26. Shuman Moss LA, Jensen-Taubman S, Stetler-Stevenson WG (2012). Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am J Pathol, 181, 1895-9. https://doi.org/10.1016/j.ajpath.2012.08.044
  27. Tadbir AA, Purshahidi S, Ebrahimi H (2012). Serum level of MMP-3 in patients with oral squamous cell carcinoma-lack association with clinico-pathological features. Asian Pac J Cancer Prev, 13, 4545-8. https://doi.org/10.7314/APJCP.2012.13.9.4545
  28. Vilen ST, Salo T, Sorsa T, Nyberg P (2013). Fluctuating roles of matrix metalloproteinase-9 in oral squamous cell carcinoma. Scientific World Journal, 2013, 920595.
  29. Wang G, Wang W, Zhou J, Yang X (2013). Correlation between telomerase activity and matrix metalloproteinases 2 expression in gastric cancer. Cancer Biomark, 13, 21-8. https://doi.org/10.3233/CBM-130332
  30. Wu ZS, Wu Q, Yang JH, et al (2008) Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer, 122, 2050-6. https://doi.org/10.1002/ijc.23337
  31. Yadav L, Puri N, Rastogi V, et al (2014). Matrix metalloproteinases and cancer - roles in threat and therapy. Asian Pac J Cancer Prev, 15, 1085-91. https://doi.org/10.7314/APJCP.2014.15.3.1085
  32. Ylisirnio S, Hoyhtya M, Turpeenniemi-Hujanen T (2000). Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. Anticancer Res, 20, 1311-6.
  33. Zhang J, Yin L, Wu J, et al (2014). Detection of serum VEGF and MMP-9 levels by Luminex multiplexed assays in patients with breast infiltrative ductal carcinoma. Exp Ther Med, 8, 175-80. https://doi.org/10.3892/etm.2014.1685

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