纤维连接蛋白及整合素β_1与人脑胶质瘤生物学行为的相关性研究

Study on the Relationships between Fibronectin, β_1 Integrin and the Biological Behaviors of Human Gliomas

目的 探讨内源性和外源性纤维连接蛋白 (fibronectin ,FN)及整合素 β1(β1integrin)在人脑胶质瘤侵袭行为和恶性进展中的作用及相互关系。方法 用细胞粘附实验和细胞迁移实验检测外源性FN和整合素 β1对U2 5 1人恶性胶质瘤细胞株粘附及迁移能力的影响。用原位杂交法检测 18例中低度恶性胶质瘤、 15例高度恶性胶质瘤及 7例正常脑组织中内源性FN和整合素 β1mRNA的表达情况。结果 ①U2 5 1细胞在外源性FN上的粘附能力呈浓度依赖性 ,尤其在中低浓度时 (<5 μg/ml)差异显著 (P <0 0 1) ;抗FN抗体及抗整合素 β1抗体均能完全阻断U2 5 1细胞在FN上的粘附。②随外源性FN浓度升高 ,U2 5 1细胞在所观察的不同时间段的迁移距离均显著增加 (P <0 0 1) ;抗FN抗体几乎完全阻断FN对细胞迁移的促进作用 ,抗整合素 β1抗体只能部分阻断FN对细胞迁移的促进作用。③细胞内FN和整合素β1mRNA在正常脑组织不表达或仅少量表达 ,而在胶质瘤中两者阳性表达率均随肿瘤恶性程度增加而增高 (P <0 0 5 ) ,且FN和整合素 β1mRNA表达呈明显正相关 (r =0 85 5 ,P <0 0 1)。结论 ①胶质瘤细胞通过其表面整合素 β1受体与外源性FN成分相互作用 ,促进其在颅内的浸润侵袭。②整合素

Objective To investigate the roles of endogenous and exogenous fibronectin (FN) and β 1 integrin in the invasion and malignant progression of human brain gliomas. Methods The influence of exogenous FN and β 1 integrin on the adhesion and migration capacity of the cells of U251 malignant glioma cell line was detected by cell adhesion assay and migration assay. Endogenous FN and integrin β 1 mRNA in 18 middle-low malignant gliomas, 15 high malignant gliomas and 7 normal brain tissues were determined by in situ hybridization. Results (1) U251 cell line showed dose-dependent adhesion to FN, especially within the extent of lower concentration (<5 μg/ml) (P<0.01). The adhesion could be blocked by anti-FN antibodies and anti-β 1 integrin antibodies; (2) The migration ability of U251 cells was enhanced by exogenous FN in a concentration-dependent manner at different time points (P<0.01). The ability was absolutely inhibited by anti-FN antibodies while partly inhibited by anti-β 1 integrin antibodies; (3) FN and β 1 integrin mRNA could hardly be seen in normal brain tissue. In gliomas the expression of FN andβ1 integrin mRNA was increased over the malignant degrees (P<0.05). The expression of FN mRNA was positively correlated with that of β 1 integrin mRNA (r=0.855, P<0.01). Conclusion (1) The interaction between exogenous FN and β 1 integrin on the cell surface contributed to the invasion of glioma cells; (2)β 1 integrin-stimulated FN synthesis was correlated to malignant degree of human gliomas. It was possible that they were positive regulators of malignant progression of gliomas.