摘要
目的细胞外基质(extracellular matrix,ECM)作为肿瘤微环境的重要组成部分,参与肿瘤的发生发展。而上皮-间质转化(epithelial-mesenchymal transition,EMT)是肿瘤细胞获得运动和侵袭能力的重要方式。本研究通过研究不同分期结直肠癌ECM的变化,探讨其对结肠癌细胞系HT29EMT的影响及作用机制。方法收集2011-01-01-2012-05-31北京朝阳医院普外科手术切除的80例结直肠癌组织和20例正常的结肠组织。应用胰酶脱细胞法制备不同分期结直肠癌ECM,并与结肠癌细胞系HT29复合培养,免疫组化和蛋白质印迹法检测不同分期结直肠癌ECM组中E-钙黏蛋白(E-cadherin,E-cad)和整合素αvβ6的表达情况。结果 E-cad主要表达于细胞膜与细胞质中,在正常结肠ECM组中强阳性表达,在结直肠癌ECM组中表达强度降低。Ⅰ期结直肠癌ECM组E-cad灰度值为1.01±0.11,Ⅱ期为1.08±0.07,Ⅲ期为1.31±0.32,Ⅳ期为1.45±0.57,均与正常结肠ECM组相比差异有统计学意义,PⅠ期=0.049,PⅡ期=0.028,PⅢ期=0.003,PⅣ期=0.001。整合素αvβ6主要表达于细胞膜,在正常结肠ECM组中低表达,在结直肠癌ECM组中表达强度增高。Ⅰ期结直肠癌ECM组整合素αvβ6表达灰度值为3.75±0.57,Ⅱ期为3.67±0.61,Ⅲ期为3.45±0.69,Ⅳ期为2.95±0.96,均与正常结肠ECM组相比差异有统计学意义,PⅠ期=0.048,PⅡ期=0.034,PⅢ期=0.014,PⅣ期=0.002。结论重构后的结直肠癌ECM具有促癌细胞发生EMT的能力;并且结直肠癌分期越高,其ECM促癌细胞发生EMT的能力越强。
OBJECTIVE Extracellular matrix is an important part of tumor microenvironment,and takes part in the occurrence and development of tumor. Epithelial-mesenchymal transition is an important way for tumor ceils to acquire the ability of movement and invasion. This study was to study the effect of the dynamic changes of extracellular matrix at the different clinical stages of CRCs on epithelial-mesenchymal transition （EMT） in human colon cancer cell line HT29. METHODS The tissues of colorectal cancer of 80 cases who received surgical excision in our hostipal from January 1st 2011 to May 31st 2012 and corresponding normal colorectal tissues were collecteded. The cells in colorectal tissues were destroyed and digested by trypsin. Extracellular matrix of different clinical stages was co-cultured with human colon cancer cell line HT29 in vitro. The expression level of E-cadherin and integrin av136 in each group was tested by immunohistochemistry and western blot. RESULTS E-cadherin was mainly expressed in the cell membrane and cytoplasm. E-cadherin was strongly expressed in the group of normal colon and its expression reduced in the groups of eoloreetal cancer. The expression level of E-cadherin in stages Ⅰ - Ⅳ colorectal cancers was lower than that in normal colonic tissue and the difference had statistical significance （P stage Ⅰ = 0. 049, Pstage Ⅱ = 0. 028, Pstage Ⅲ = 0. 003, Ptage Ⅳ = 0. 001, Integrin αvβ6 was mainly expressed in the cell membrane. The expression of integrin αvβ6 was low in group of normal colon and high in the groups of colorectal cancer tissues. The expression level of Integrin αvβ6 in stages Ⅰ -- Ⅳ colorectal cancers was higher than that in normal colonic tissue and the difference had statistical significance （P stage Ⅰ = 0. 048, Pstage Ⅱ = 0. 034, Pstage Ⅲ = 0. 014,Pstage Ⅳ = 0. 002）. CONCLUSIONS Compared with ECM of normal colonic tissues,the remodeled ECM of colorectal cancer tissues was more conducive to induce EMT. The ability to promote EMT was enha
出处
《中华肿瘤防治杂志》
CAS
北大核心
2016年第16期1076-1080,共5页
Chinese Journal of Cancer Prevention and Treatment
关键词
结直肠癌
细胞外基质
肿瘤微环境
上皮-间质转化
colorectal cancer
extracellular matrix
tumor microenvironment
epithelial-mesenchymal transition
