title: Matrix metalloproteinase-9,-3 and tissue inhibitor of matrix metalloproteinase-1 in colorectal cancer: relationship to clinicopathological variables.
abstract: The balance between matrix metalloproteinases (MMPs) and their physiological tissue inhibitors of matrix metalloproteinases (TIMPs) is crucial in tumour invasion and progression. The aim of this study was to investigate the levels of MMP-9, MMP-3 and TIMP-1 in colorectal cancer (CRC) and to evaluate these proteinases and their inhibitor with respect to clinicopathological variables. Activities of pro- and active MMP-9 were measured in paired tumour and distant normal tissue specimens from 43 patients with CRC using gelatin zymography. ELISA was employed for the determination of MMP-9, MMP-3 and TIMP-1 protein expressions. The activity levels of pro- and active MMP-9 and protein expression levels of MMP-9, MMP-3 and TIMP-1 were higher in tumour tissues than in the corresponding normal tissues; the differences being significant for all (p < 0.05), except TIMP-1. Similarly, active MMP-9/proMMP-9 and the ratio of protein expression level of MMP-9-TIMP-1 were found to be significantly higher in tumour tissues ( p < 0.01). Among all the clinicopathological variables investigated, significant correlations were found between MMP-9 and presence of perineural invasion, MMP-3 and lymph node status, TIMP-1 and tumour differentiation, MMP-9/TIMP-1 ratio and histological types ( p < 0.05). In conclusion, MMP-3 was not as notably increased as MMP-9 in tumour tissues. However, different roles may be attributed to MMP-9 and MMP-3 in CRC development and progression. Additionally, assessment of TIMP-1 in relation to MMPs appeared to be crucial in CRC studies to provide a basis for the re-evaluation of the clinical usefulness of TIMP-1 in colorectal cancer.
authors.affiliation: Department of Biochemistry, School of Medicine, Dokuz Eylül University, Inciralti, Izmir Turkey. huray.islekel@deu.edu.tr
authors.forename: Hüray
authors.initials: H
authors.lastname: Işlekel
authors.forename: Gülgün
authors.initials: G
authors.lastname: Oktay
authors.forename: Cem
authors.initials: C
authors.lastname: Terzi
authors.forename: Aras Emre
authors.initials: AE
authors.lastname: Canda
authors.forename: Mehmet
authors.initials: M
authors.lastname: Füzün
authors.forename: Ali
authors.initials: A
authors.lastname: Küpelioğlu
mesh_terms: D000368:Aged; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000503:physiopathology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012007:Rectum / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9