口腔鳞癌中血管内皮生长因子和明胶酶-A的表达及低氧调节

Expression and hypoxic regulation of vascular endothelial growth factor and matr ix metalloproteinase-2 in oral squamous cell carcinoma

目的 研究血管内皮生长因子 (VEGF)和明胶酶 -A(matrixmetalloproteinase -2 ,MMP -2 )的表达与口腔鳞癌血管形成和临床的关系 ,以及低氧对其调节作用。方法 应用SABC免疫组化染色的方法检测 40例口腔鳞癌手术标本中VEGF、MMP -2的表达和微血管密度 (MVD) ,用酶联免疫吸附实验 (ELISA )的方法定量测定了低氧对口腔鳞癌TSCCa细胞系和颈淋巴转移癌GNM细胞系中VEGF和MMP -2活性的影响。结果 口腔鳞癌中VEGF、MMP -2的表达显著高于正常口腔黏膜组织 ,与肿瘤内MVD密切正相关 (P <0 .0 5 ) ,VEGF、MMP-2表达和口腔鳞癌中的MVD计数与口腔鳞癌病理分级和临床分期无关 ,与口腔鳞癌颈淋巴结转移密切相关 (P<0 .0 5 )。低氧可以显著增加口腔鳞癌细胞TSCCa细胞系和颈淋巴转移癌GNM系中VEGF和MMP -2的活性。结论 VEGF和MMP -2的表达可能在口腔鳞癌血管形成和转移中起重要作用 ,并受低氧调节 ,VEGF与MMP -2可能具有某种内在联系 ,有可能作为反映口腔鳞癌侵袭转移的生物学指标和抗血管治疗的靶点。

Objective To investigate the ex pression and hypoxic regulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2. Method The expression of VEGF and MMP-2 protein and microvessel de nsity (MVD) in 40 cases oral squamous cell carcinoma were examined by SABC immunohistichemical st ain. The effect of hypoxia on the activities of VEGF and MMP-2 in oral squamous cell carcinoma cell lines TSCCa and metastasis carcinoma cell lines GNM was quan titatively determined by enzyme linked immunosorbent assay (ELISA). Resu lt The expression of VEGF and MMP-2 in oral squamous cell carcinoma, being significant ly correlated with MVD in the tumor, was remarkably higher than in the normal or al mucosa member. VEGF 、MMP-2 and MVD in the tumor was unassociated with clinic al stage and pathological grade of oral squamous cell carcinoma, while was assoc iated with neck lymph node metastasis. Hypoxia significantly increased the activ ity of VEGF and MMP-2 in oral squamous cell carcinoma cell lines TSCCa and metas tasis carcinoma cell lines GNM. Conclusion the expression of VEGF and MMP-2 pl ay an important role in the angiogenesis and metastasis of oral squamoua cell ca rcinoma, which is regulated by hypoxia. There may be relationship between VEGF a nd MMP-2 in the process of metastasis of oral squamoua cell carcinoma, VEGF and MMP-2 may serve as a predictor of metastasis and a potential target for antiangi ogenic therapy of oral squamoua cell carcinoma.