The present study aimed to detect comparative expression of integrin αVβ3 and its involvement in expression and activation of matrix metalloproteinase-2 (MMP-2) in 25 malignant human breast tumor and adjacent normal...The present study aimed to detect comparative expression of integrin αVβ3 and its involvement in expression and activation of matrix metalloproteinase-2 (MMP-2) in 25 malignant human breast tumor and adjacent normal breast tissues from different clinical TNM stages (DCIS to T4) of the disease and possible involvement of known regulating parameters of MMP-2 like TIMP-2, MT1-MMP and EMPRIN. Integrin αVβ3 was highly expressed in tumors than adjacent normal breast tissues. Pro-MMP-2(72-KD) was mainly expressed in adjacent normal tissues compared to tumors. The mature forms of MMP-2 (68 KD and 64 KD) were found only in tumors. Appreciable expression of TIMP-2 and induction of MT1-MMP and EMPRIN in T2-T4 stages suggested their possible role in MMP-2 activation. Over expression Integrin αVβ3 in tumors than adjacent normal breast tissues was an indication of cancer progression with involvement of integrin signaling. We conclude that, the co-precipitation of MMP-2 with αvβ3 by anti-αv antibody is a strong indication that integrin αvβ3 is a surface receptor for MMP-2 and αvβ3-MMP-2 complex on the surface of tumor cells may play a very important role in determining the invasive property and malignant behavior of tumor tissues. The positive expression of endogenous inhibitor of MMP-2, TIMP-2 may have an appreciable role in activation of this protease and risk of malignancy in advanced stage of the disease. The enhanced expression of MT1-MMP and EMPRIN suggested a role for these factors in gelatinase regulation. However the exact mechanism(s) remains to be investigated. Finally, evaluation of integrin αVβ3 associated MMP-2 expression and activity may add valuable information and can possibly be therapeutic target. The clinical exploitation of integrins will provide oncologists with novel therapeutic strategies for the treatment of malignancy in breast cancer.展开更多
目的 探讨整合素αvβ3、趋化因子受体（CXC chemokine receptor,CXCR）4、CXCR7在头颈部鳞状细胞癌（squamous cell carcinoma of head and neck,SCCHN）及颈淋巴结组织中的表达及其在淋巴结转移中的作用.方法 收集2010年1月至2015年1...目的 探讨整合素αvβ3、趋化因子受体（CXC chemokine receptor,CXCR）4、CXCR7在头颈部鳞状细胞癌（squamous cell carcinoma of head and neck,SCCHN）及颈淋巴结组织中的表达及其在淋巴结转移中的作用.方法 收集2010年1月至2015年1月郑州大学附属肿瘤医院头颈甲状腺外科92例SCCHN,应用免疫组织化学SABC法检测SCCHN、淋巴结转移灶、正常淋巴结以及正常黏膜组织中整合素αvβ3、CXCR4和CXCR7的表达情况.结果 整合素αvβ3、CXCR4和CXCR7主要表达于SCCHN的胞质和胞膜,三者在SCCHN原发灶中阳性表达率分别为75％（69/92）、82％（75/92）和76％（70/92）,在淋巴结转移灶中阳性表达率分别为81％（75/92）、76％ （70/92）和65％（60/92）.整合素αvβ3、CXCR4在SCCHN原发灶（r=0.813,P＜0.05）和淋巴结转移中（r=0.541,P＜0.05）的表达呈正相关;整合素αvβ3及CXCR7在SCCHN原发灶（r=0.683,P＜0.05）和淋巴结转移中（r=0.708,P＜0.05）的表达呈正相关;CXCR4、CXCR7在SCCHN原发灶（r=0.644,P＜0.05）和淋巴结转移中（r=0.707,P＜0.05）的表达呈正相关.整合素αvβ3、CXCR4和CXCR7表达的强弱与肿瘤大小（P=0.040、0.001、0.009）、淋巴结转移（P=0.001、0.000、0.000）、有无周围组织侵犯（P=0.046、0.002、0.001）显著相关,与患者年龄（P=0.097、0.274、0.162）、性别（P=0.103、0.309、0.187）无关.结论 整合素αvβ3、CXCR4、CXCR7在SCCHN原发灶组织及转移淋巴结中呈高表达,并与淋巴转移显著相关,三者可能共同促进SCCHN的淋巴结转移.展开更多
文摘The present study aimed to detect comparative expression of integrin αVβ3 and its involvement in expression and activation of matrix metalloproteinase-2 (MMP-2) in 25 malignant human breast tumor and adjacent normal breast tissues from different clinical TNM stages (DCIS to T4) of the disease and possible involvement of known regulating parameters of MMP-2 like TIMP-2, MT1-MMP and EMPRIN. Integrin αVβ3 was highly expressed in tumors than adjacent normal breast tissues. Pro-MMP-2(72-KD) was mainly expressed in adjacent normal tissues compared to tumors. The mature forms of MMP-2 (68 KD and 64 KD) were found only in tumors. Appreciable expression of TIMP-2 and induction of MT1-MMP and EMPRIN in T2-T4 stages suggested their possible role in MMP-2 activation. Over expression Integrin αVβ3 in tumors than adjacent normal breast tissues was an indication of cancer progression with involvement of integrin signaling. We conclude that, the co-precipitation of MMP-2 with αvβ3 by anti-αv antibody is a strong indication that integrin αvβ3 is a surface receptor for MMP-2 and αvβ3-MMP-2 complex on the surface of tumor cells may play a very important role in determining the invasive property and malignant behavior of tumor tissues. The positive expression of endogenous inhibitor of MMP-2, TIMP-2 may have an appreciable role in activation of this protease and risk of malignancy in advanced stage of the disease. The enhanced expression of MT1-MMP and EMPRIN suggested a role for these factors in gelatinase regulation. However the exact mechanism(s) remains to be investigated. Finally, evaluation of integrin αVβ3 associated MMP-2 expression and activity may add valuable information and can possibly be therapeutic target. The clinical exploitation of integrins will provide oncologists with novel therapeutic strategies for the treatment of malignancy in breast cancer.
文摘目的 探讨整合素αvβ3、趋化因子受体（CXC chemokine receptor,CXCR）4、CXCR7在头颈部鳞状细胞癌（squamous cell carcinoma of head and neck,SCCHN）及颈淋巴结组织中的表达及其在淋巴结转移中的作用.方法 收集2010年1月至2015年1月郑州大学附属肿瘤医院头颈甲状腺外科92例SCCHN,应用免疫组织化学SABC法检测SCCHN、淋巴结转移灶、正常淋巴结以及正常黏膜组织中整合素αvβ3、CXCR4和CXCR7的表达情况.结果 整合素αvβ3、CXCR4和CXCR7主要表达于SCCHN的胞质和胞膜,三者在SCCHN原发灶中阳性表达率分别为75％（69/92）、82％（75/92）和76％（70/92）,在淋巴结转移灶中阳性表达率分别为81％（75/92）、76％ （70/92）和65％（60/92）.整合素αvβ3、CXCR4在SCCHN原发灶（r=0.813,P＜0.05）和淋巴结转移中（r=0.541,P＜0.05）的表达呈正相关;整合素αvβ3及CXCR7在SCCHN原发灶（r=0.683,P＜0.05）和淋巴结转移中（r=0.708,P＜0.05）的表达呈正相关;CXCR4、CXCR7在SCCHN原发灶（r=0.644,P＜0.05）和淋巴结转移中（r=0.707,P＜0.05）的表达呈正相关.整合素αvβ3、CXCR4和CXCR7表达的强弱与肿瘤大小（P=0.040、0.001、0.009）、淋巴结转移（P=0.001、0.000、0.000）、有无周围组织侵犯（P=0.046、0.002、0.001）显著相关,与患者年龄（P=0.097、0.274、0.162）、性别（P=0.103、0.309、0.187）无关.结论 整合素αvβ3、CXCR4、CXCR7在SCCHN原发灶组织及转移淋巴结中呈高表达,并与淋巴转移显著相关,三者可能共同促进SCCHN的淋巴结转移.
