摘要
目的研究整合素αvβ3、黏着斑激酶(FAK)、纤连蛋白(FN)和基质金属蛋白酶-9(MMP-9)在结直肠癌转移中的作用机制。方法应用半定量逆转录聚合酶链反应(SQRT-PCR)和免疫组织化学方法,检测30例结直肠癌标本中整合素αvβ3、FAK、FN和MMP-9mRNA转录水平和蛋白表达变化。结果结直肠癌组织中整合素αvβ3亚基转录水平明显增高(P<0.05),FAK、FN和MMP-9mRNA转录水平随肿瘤浸润深度增加和Dukes分期进展而升高(P<0.05),且在淋巴结转移组升高明显(P<0.05);FAK和细胞外基质中FN、MMP-9蛋白表达水平与其基因mRNA转录水平改变相一致,但基底膜上的FN蛋白表达改变则完全相反。结论结直肠癌细胞转移初始阶段,FN-整合素αvβ3-细胞骨架-FAK系统由细胞外向细胞内传递信号,产生MMP-9等因子,完成癌细胞脱落、黏附、降解、转移的过程,且上述基因的转录、表达水平越高,结直肠癌的侵袭转移潜能越强。
Objective To study the roles of integrin αvβ3,focal adhesin kinase,fibronectin,matrix metalloproteinase 9 in the metastasis of colorectal cancer. Methods Tumor and paratumor specimens from 30 colorectal cancer patients were used in the study. Immunohistochemical staining and semiquantitative reverse transcription polymerase chain reaction were used to determine the transcription and expression of integrin αvβ3,FAK,FN,MMP 9 (SQRT PCR). Results The mRNA transcription level of integrin αvβ3 in colorectal cancer tissue was obviously higher than that in paratumor normal tissues(P< 0.05). The mRNA transcriptions of FAK,FN,MMP 9 were obviously increased with the progress of tumor invasion and Dukes stage(P< 0.05),which could also be found in cases with lymph node metastasis(P< 0.05). Expression of FAK,FN in extracellular matrix(ECM),MMP 9 was accorded with their transcription,however,expression of FN protein in basement membrane was negatively correlated. Conclusions At the early stage of the metastasis of colorectal cancer,the FN integrin αvβ3 cytoskeleton FAK system transfers signals from ECM to cell and induces the production of MMP 9 and other factors,resulting in the disengaging,adhering,degrading,metastasis of cancer cells. The mRNA transcriptions and expression of the above genes are accordant with the invasive ability of colorectal cancer.
出处
《中华胃肠外科杂志》
CAS
2004年第6期456-459,共4页
Chinese Journal of Gastrointestinal Surgery
关键词
整合素
信号转导因子
结肠癌
直肠癌
转移
作用机制
Colorectal neoplasms
Neoplasm metastasis
Integrin alpha v beta 3
Focal adhesin kinase
Fibronectin
Matrix metalloproteinase 9
