| Background and intentionInfiltration and metastasis of a malignant tumor is a complicated process that maybe involves many factors as invasion and adhesion of tumor cells,interaction between tumor cells and mesenchyma.67 kD laminin receptor(67LR) is a non-integrin receptor of laminin.It is such a multifunctional protein that not only participate the process of ribosome's assembling and maturity but also involve the signal transduction of cells,moreover it acts membrane receptor of diverse kinds of virus.67LR can promote the carcinoma's infiltration and metastasis by interacting with laminin,regulating the tumor's multiplication and adhesion,forming the capillary vessels,accelerating the degradation of extracellular matrix(ECM).67LR has highly expression in many kinds of tumors.Matrix metalloproteinases(MMPs) is a family of zinc dependent enzymes that cleave various components of extracellular matrix(ECM) as collagenases,gelatinases, stromelysins.MMP-7 is the smallest member of the family,which expresses in tumor cell and can activate the other members,and has broad-spectrum degradation to ECM. It expresses in tumor cells frequently and operates significantly in generation and evolution of tumors,while acts intimately on infiltration and metastasis of tumor cellsTissue inhibitor of matrix metalloproteinases(TIMPs) are the selective inhibitors of MMPs.Among all TIMPs,TIMP-1 has the strongest effect.TIMP-1 can inhibit the activity of MMP-7 by forming steady complex as MMP-7's natural inhibitor,then has negative regulation in degradation to ECM,inhibiting infiltration and metastasis of tumor;however TIMP-1 can promote the generation and metastasis of tumor cells just as a kind of growth factor.The morbidity of esophageal squamous cell carcionma(ESCC) is higher in the worldwide malignant tumors.It is relatively common in East Asians such as China and Japan,the 5-year-aftertreatment survival rate of ESCC was only 20%～36%. Infiltration and metastasis are the essential biological feature of the malignant tumors, also the key factors of leading to death in sufferers of ESCC.So exploring the mechanism of the invasion and metastasis of ESCC has become one of research hot spots.To this date,domestic and foreign documents have no report on co-researches in expression and significance of 67LR,MMP-7 and TIMP-1 in ESCC.In order to discuss the mechanisms of infiltration and metastasis of ESCC and search valid methods which can suppress the infiltration and metastasis,this research adopts immunohistochemistry SP method to observe the expression of 67LR,MMP-7 and TIMP-1 in 56 cases of ESCC tissues,26 cases of adjacent non-atypical hyperplasia tissues and 23 cases of normal epithelium of mucosa.Detecting unitedly illuminates furtherly the mechanisms of infiltration and metastasis of ESCC and provides theory foundation for blocking infiltration and metastasis of ESCC.Methods1.Using the immunohistochemistry SP technology to detect the expression of 67LR, MMP-7 and TIMP-1 in 56 cases of ESCC tissues,26 cases of adjacent atypical hyperplasia tissues and 23 cases of normal epithelium of mucosa respectively.2.Statistical analysis:All the data were analyzed by SPSS 13.0 statistical package. The Chi-square was used in the comparison of positive rates;relations of two variables were analyzed by the spearman level correlation analysis.The level of significant difference wasα=0.05.Results1.The expression rates of 67LR protein in normal epithelium of esophageal mucosa, atypical hyperplasia tissues,and carcinoma tissues were 13.04%(3/23),53.85%(14/26) and 67.86%(38/56) respectively;the positive expression rate of 67LR protein in the carcinoma tissues was compared with that in the normal mucosa tissues,there was statistical significance(P＜0.01).So was compare of the atypical hyperplasia tissues with the normal mucosa tissues(P＜0.01);The positive expression rates of MMP-7 protein in normal mucosa of esophagus,atypical hyperplasia tissues,and carcinoma tissues were 34.78%(8/23),76.92%(20/26) and 73.21%(41/56) respectively;the positive expression rate of MMP-7 protein in the carcinoma tissues was compared with that in the normal mucosa tissues,there was statistical significance(P＜0.01).So was comparing of the atypical hyperplasia tissues with the normal mucosa tissues(P＜0.01);The positive expression rates of TIMP-1 protein in normal mucosa, atypical hyperplasia tissues and carcinoma tissues were 0%(0/23),19.23%(5/26)and 42.86%(24/56) respectively,the positive expression rate of TIMP-1 protein in the carcinoma tissues was compared with that in the propotional adjacent tissues and normal mucosa tissues from each other,there was statistical significance(P＜0.05).2.In the tissues of ESCC,the positive rates of expression on the submucous layer invaded,low-muscle invaded,deep-muscle invaded and outer layer invaded,67LR were 66.67%(2/3),80.00%(12/15),50.00%(10/20)and 77.78%(14/18) respectively, compared with each other of different layer invaded,there was no significance (P＞0.05);The positive rates of expression of MMP-7 protein on the 3 layers invaded mentioned above were 33.33%(1/3),46.67%(7/15),85.00%(17/20)and 88.89%(16/18) respectively,the expression of MMP-7 in the carcinoma tissues of submucous layer invaded was compared with deep-muscle invaded and outer layer invaded, low-muscle invaded was compared with deep-muscle invaded and outer layer invaded, there were significant difference among the groups(P＜0.05);The positive rates of expression of TIMP-1 protein on the 3 layers invaded mentioned above were 66.67%(2/3),60.00%(9/15),55.00%(11/20)and 11.11%(2/18) respectively,the expression of TIMP-1 in the carcinoma tissues with the outer layer invaded was evidently lower than that in the tissues of submucous layer invaded,low-muscle invaded and deep-muscle invaded.There was significant difference among the groups(P＜0.05).3.In the 26 cases of lymph node metastasis group,the positive rate of expression of 67LR protein in the tumor tissues was 84.62%(22/26);In the 30 cases of non-metastatic group,it was 53.33%(16/30),there was significant difference between the two groups(P＜0.05).In the 26 cases of lymph node metastasis group,the positive rate of expression of MMP-7 protein in the tumor tissues was 92.31%(24/26);In the 30 cases of non-metastatic group,it was 56.67%(17/30),there was significant difference between the two groups(P＜0.01).In the 26 cases of lymph node metastasis group,the positive rate of expression of TIMP-1 protein in the tumor tissues was 23.08%(6/26);in the non-metastatic group,it was 60.00%(18/30),there was significant difference between the two groups(P＜0.01)4.Relativities of the expression of 67LR,MMP-7 and TIMP-1 in ESCC were analyzed statistically.Results showed that the expression of 67LR was positively correlated with that of MMP-7,negatively correlated with that of TIMP-1(P＜0.0 5). The expression of MMP-7 had no correlation with TIMP-1(P＞0.05).Conclusions1.It indicated that 67LR,MMP-7 and TIMP-1 protein participated in occurrence and development of ESCC possibly.2.It indicated that there was no correlation between the expression of 67LR protein and invasion of ESCC,there was correlation between the expression of MMP-7 and TIMP-1 protein and invasion of ESCC.3.It indicated that there was correlation between the expression of 67LR protein, MMP-7 protein and TIMP-1 protein and metastasis of ESCC.4.Results showed that the expression of 67LR was positively correlated with that of MMP-7,negatively correlated with that of TIMP-1.The expression of MMP-7 had no correlation with TIMP-1.It showed 67LR,MMP-7 and TIMP-1 protein played a synergistic effect during the process of occurrence and development and infiltration, metastasis of ESCC probably. |
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