The Expression And Significance Of MMP-1, MMP-13 And TIMP-4 In Larngeal Carcinoma

Objective:Matrix metalloproteinase(MMPs)and tissue inhibitor of metalloproteinases(TIMPs)are two of the most important proteolytic enzymes involving in the regulative process of the synthesis and degradation of the basement membranes(BM)and extracellular matrix (ECM).The degradation of BM and ECM is a key step related to the invasion and metastasis carcinoma.MMP-1 and MMP-13 which belong to collagenase can degrade BM and ECM,TIMP-4 which is a new member of TIMPs family can integrate with MMPs to form a 1:1 complex thus inhibit the activity of the latter.So the objective is to study the expression of MMP-1,MMP-13 and TIMP-4 in laryngeal carcinoma, to discuss the relationship between the three enzymes and the invasion and metastasis of laryngocarcinoma,and then to look for some tumor markers which might prognose the invasion and metastasis of laryngeal carcinoma to be used in clinical.Method:The technique of tissue microarray and immunohistochemistry was applied to detect the expressions of MMP-1, MMP-13 and TIMP-4 in 50 pairs of laryngeal carcinoma tissues and adjacent tissues;the technique of fluorescent quantitation RT-PCR was applied to detect the expressions of MMP-1,MMP-13 and TIMP-4 in 22 paires of laryngeal carcinoma tissues and adjacent tissues.According to 2002 TNM staging made by UICC,the tissues of laryngeal carcinoma were divided into T₁+T₂ group and T₃+T₄ group,as well as non metastasis group(LN-)and metastasis group(LN+)to compare.Results:(1)The expression rate of MMP-1 protein(75.5%)was higher than that of adjacent tissues(2.2%),Group T₁+T₂ was lower than that of T₃+T₄,Group LN- was lower than that of LN+(P＜0.05).The relative expressions of MMP-1 mRNA of laryngeal carcinoma tissues (2.005±0.758)was higher than that of adjacent tissues(0.476±0.350) (P＜0.05);the differences between Group T₁+T₂ and Group T₃+T₄,Group LN- and Group LN+ had no statistically significance, respectively.(P＞0.05).(2)The expression rate of MMP-13 protein(40.8%) was higher than that of adjacent tissues(2.4%),Group T₁+T₂ was lower than that of T₃+T₄,Group LN- was lower than that of LN+(P＜0.05).The relative expressions of MMP-13 mRNA of laryngeal carcinoma tissues(0.604±0.389)was higher than that of adjacent tissues (0.160±0.101)(P＜0.05);the differences between Group T₁+T₂ and Group T₃+T₄,Group LN- and Group LN+ had no statistically significance,respectively(P＞0.05).(3)The expression rate of TIMP-4 protein of laryngeal carcinoma tissues(16.0%)was lower than that of adjacent tissues(51.6%),Group T₁+T₂ was higher than that of T₃+T₄, Group LN- was higher than that of LN+(P＜0.05).The relative expressions of TIMP-4 mRNA of laryngeal carcinoma tissues (0.342±0.243)was lower than that of adjacent tissues(0.814±0.459); Group T₁+T₂ was lower than that of T₃+T₄,Group LN- was lower than that of LN+(P＜0.05).Conclusions:(1)100-spots laryngeal carcinoma tissue microarrays was successfully constructed,the mean effectivity of them was 93%.(2) The expression of MMP-1 and MMP-13 in laryngeal carcinoma tissues upregulate,and the expression of TIMP-4 downragulate,which might be of great value in the diagnosis of laryngeal carcinoma.(3)The MMP-1 and MMP-13 were highly expressed in Group T₃+T₄ and Group LN+, these two proteases might promote the invasion and metastasis of laryngeal carcinoma,which might be of great value in the determination of therapeutic regimens and prognosis of laryngeal carcinoma.(4)The expression of TIMP-4 and its mRNA were high in Group T1+T2 and Group LN-,which suggest that TIMP-4 might play a role in the suppression of the invasion and metastasis of laryngeal carcinoma,and then pave a way for finding a new antitumor drug.