Expression of matrix metalloproteinases (MMPs) and their inhibitor (TIMP) genes on mRNA and protein levels in oral squamous cell carcinoma
Streszczenie
Introduction. To investigate the mRNA and protein expression of MMP-2, MMP-9, MMP-7 and their tissue inhibitor TIMP-2 in tissue specimens with oral squamous cell cancer (OSCC) and in healthy tissues.
Material and methods. The expression genes of MMP-2, MMP-9, MMP-7 and TIMP-2 on mRNA levels were detected by the RT-PCR method in 31 samples with oral squamous cell carcinoma and in 31 healthy, control tissues. Secondly, the concentration of the analysed metalloproteinases and their inhibitor was assessed in tumor and non-tumor tissues using the enzyme-linked immunosorbent assay (ELISA) method.
Results. The mean values of gene expression of MMP-2, MMP-7, MMP-9 and TIMP in tissues with oral squamous cell cancer were significantly higher in comparison to normal ones (p < 0.0001). Similar observations were found for concentration levels of analysed MMPs and TIMP in tissues with and without oral cancer (p < 0.0001).
Conclusions. The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 gene expression on protein and mRNA levels is higher in oral squamous cell carcinoma tissues than in healthy control tissues. This may suggest that MMPs and TIMP play an important role in tumorogenesis. We did not observe any correlation between the clinicopathological characteristics of patients with OSCC and expression levels of MMPs and TIMP.
Słowa kluczowe: ELISAenzyme assaysoral cancermetalloprteinases
Referencje
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- Aebersold DM, Beer KT, Laissue J, et al. Intratumoral microvessel density predicts local treatment failure of radically irradiated squamous cell cancer of the oropharynx. Int J Radiat Oncol Biol Phys. 2000; 48(1): 17–25.
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- Impola U, Cuccuru MA, Masala MV, et al. Preliminary communication: matrix metalloproteinases in Kaposi's sarcoma. Br J Dermatol. 2003; 149(4): 905–907.
- Impola U, Toriseva M, Suomela S, et al. Matrix metalloproteinase-19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation. Int J Cancer. 2003; 103(6): 709–716.
- Murray GI. Matrix metalloproteinases: a multifunctional group of molecules. J Pathol. 2001; 195(2): 135–137, doi: 10.1002/1096-9896(200109)195:2<135::AID-PATH939>3.0.CO;2-G.
- Jayade BV, Bhat K, Patil BR, et al. Histological significance of p53 gene expression in squamous cell carcinoma of the buccal mucosa. J Maxillofac Oral Surg. 2009; 8(3): 205–210.
- Amar S, Smith L, Fields GB. Matrix metalloproteinase collagenolysis in health and disease. Biochim Biophys Acta Mol Cell Res. 2017; 1864(11 Pt A): 1940–1951.
- Luukkaa M, Vihinen P, Kronqvist P, et al. Association between high collagenase-3 expression levels and poor prognosis in patients with head and neck cancer. Head Neck. 2006; 28(3): 225–234.
- Mishev G, Deliverska E, Hlushchuk R, et al. Prognostic value of matrix metalloproteinases in oral squamous cell carcinoma. Biotechnol Biotechnol Equip. 2014; 28(6): 1138–1149.
- Ranuncolo SM, Matos E, Loria D, et al. Circulating 92-kilodalton matrix metalloproteinase (MMP-9) activity is enhanced in the euglobulin plasma fraction of head and neck squamous cell carcinoma. Cancer. 2002; 94(5): 1483–1491.
- Basset P, Bellocq JP, Wolf C, et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990; 348(6303): 699–704.
- 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. 2005; 131(6): 340–346.
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- Thomas GT, Lewis MP, Speight PM. Matrix metalloproteinases and oral cancer. Oral Oncol. 1999; 35(3): 227–233.
- Yorioka CW, Coletta RD, Alves F, et al. Matrix metalloproteinase-2 and -9 activities correlate with the disease-free survival of oral squamous cell carcinoma patients. Int J Oncol. 2002; 20(1): 189–194.
- Rautava J, Luukkaa M, Heikinheimo K, et al. Squamous cell carcinomas arising from different types of oral epithelia differ in their tumor and patient characteristics and survival. Oral Oncol. 2007; 43(9): 911–919.
- Tang Yi, Nakada MT, Kesavan P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 2005; 65(8): 3193–3199.
- Imanishi Y, Fujii M, Tokumaru Y, et al. Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma. Hum Pathol. 2000; 31(8): 895–904.
- Patel BP, Shah PM, Rawal UM, et al. Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma. J Surg Oncol. 2005; 90(2): 81–88.
- Impola U, Jeskanen L, Ravanti L, et al. Expression of matrix metalloproteinase (MMP)-7 and MMP-13 and loss of MMP-19 and p16 are associated with malignant progression in chronic wounds. Br J Dermatol. 2005; 152(4): 720–726.
- Mimori K, Yamashita K, Ohta M, et al. Coexpression of matrix metalloproteinase-7 (MMP-7) and epidermal growth factor (EGF) receptor in colorectal cancer: an EGF receptor tyrosine kinase inhibitor is effective against MMP-7-expressing cancer cells. Clin Cancer Res. 2004; 10(24): 8243–8249.
- American Joint Committee on Cancer: AJCC. www.cancerstaging.org (10.02.2018).
- Union for International Cancer Control (UICC). www.uicc.org (10.02.2018).
- Kapral M, Strzałka-Mrozik B, Paluch J, et al. Evaluation of gene expression of selected matrix metalloproteinases and their tissue inhibitors in laryngeal cancer. Farm Przegl Nauk. 2010; 10: 41–46.
- Xie M, Sun Y, Li Y. Expression of matrix metalloproteinases in supraglottic carcinoma and its clinical implication for estimating lymph node metastases. Laryngoscope. 2004; 114(12): 2243–2248.
- Zhang H, Liu M, Sun Y, et al. MMP-14 can serve as a prognostic marker in patients with supraglottic cancer. Eur Arch Otorhinolaryngol. 2009; 266(9): 1427–1434.
- Grzelczyk WL, Wróbel-Roztropiński A, Szemraj J, et al. [The matrix metalloproteinase in oral and oropharyngeol cancer - literature review]. Postepy Biochem. 2016; 62(4): 506–510.
- Singh RD, Nilayangode H, Patel JB, et al. Combined evaluation of matrix metalloproteinases and their inhibitors has better clinical utility in oral cancer. Int J Biol Markers. 2011; 26(1): 27–36.
- Roomi MW, Monterrey JC, Kalinovsky T, et al. Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol Rep. 2009; 21(5): 1323–1333.
- Hong Qu, Jun T, Lei J, et al. Expression and Clinical Significance of Matrix Metalloproteinase-2 and Its Inhibitor TIMP-2 in Oral Squamous Cell Carcinoma. J Hard Tissue Biol. 2006; 15(2): 54–60.
- Kawamata H, Uchida D, Hamano H, et al. Active-MMP2 in cancer cell nests of oral cancer patients: correlation with lymph node metastasis. Int J Oncol. 1998; 13(4): 699–704.
- Ikebe T, Shinohara M, Takeuchi H, et al. Gelatinolytic activity of matrix metalloproteinase in tumor tissues correlates with the invasiveness of oral cancer. Clin Exp Metastasis. 1999; 17(4): 315–323.
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- de Vicente JC, Fresno MF, Villalain L, et al. Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma. Oral Oncol. 2005; 41(3): 283–293.
- Overall CM, Kleifeld O. Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006; 6(3): 227–239.