原代癌相关成纤维细胞和正常成纤维细胞特征比较及对结直肠癌细胞EMT影响  

Characteristics of Primary Cancer Associated Fibroblasts and Normal Fibroblasts and Their Effects on Colorectal Cancer EMT

作　　者：聂倩倩[1] 朱紫菱 姜支农[2] 邓红[1] 

机构地区：[1]浙江大学医学院病理学与病理生理学系 杭州市310058 [2]浙江大学医学院附属邵逸夫医院病理科 杭州市310020

出　　处：《医学分子生物学杂志》2016年第3期136-142,共7页Journal of Medical Molecular Biology

基　　金：浙江省自然科学基金（No.LY12H16027）,国家自然科学基金（No.30870971）,浙江省卫生厅项目（No.2016KYB141）

摘　　要：目的：观察原代癌相关成纤维细胞（ cancer associated fibroblasts， CAFs）和正常成纤维细胞（ normal fibroblasts， NFs）特征及其对结直肠癌细胞SW620上皮间质转化（ epithelial？mesenchymal transition， EMT）的影响。方法鉴定 NFs和 CAFs，比较两者活化和衰老程度。通过间接共培养实验观察两者对SW620细胞EMT和迁移能力影响。结果 NFs 和 CAFs 表达纤连蛋白（ Fibronectin ）和α？平滑肌动蛋白（α？smooth muscle actin，α？SMA），不表达 E？钙黏蛋白（E？Cadherin）。 CAFsα？SMA 表达和衰老程度高于NFs。 CAFs促进SW620细胞E？Cadherin下调、波形蛋白（ vimentin）和Fibronectin上调， Wnt信号蛋白磷酸化的β？连环蛋白（Ser552， S552）和蓬乱蛋白（Dishevelled 3， DVL3）上调，促进其迁移。 NFs对SW620细胞EMT和迁移能力无影响。结论 CAFs活化和衰老程度大于NFs； CAFs促进结直肠癌细胞EMT、迁移和Wnt信号上调； NFs对结直肠癌细胞EMT和迁移能力无影响。Objective To explore the characteristics of primary cancer associated fibroblasts （CAFs） and normal fibroblasts （NFs） and their effects on the epithelial？mesenchymal transition （ EMT） of colorectal cancer （ CRC ） cells. Methods CAFs and NFs were cultured and identi？fied. The viability and senescence were compared between CAFs and NFs. The effects of the two types of cells on the EMT and migrating ability of SW620 cells were examined by indirect coculture method. Results Both of NFs and CAFs were found to express fibronectin and α？SMA but not E？cadherin. The α？SMA expression and the senescence were greater in CAFs than in NFs. CAFs in？duced the EMT and migration of CRC cells by down？regulating E？cadherin and up？regulating vimen？tin and fibronectin. The expression levels of phospho？β？catenin （ Ser552 , S552 ） and dishevelled 3 （ DVL3 ） were up？regulated after CAFs treatment. NFs had no effect on the EMT and migration of SW620 cells. Conclusion The viability and senescence of CAFs were greater than those of NFs. CAFs promote the EMT, migration and up？regulation of Wnt signaling in CRC cells. NFs have no effects on the EMT and migration of CRC cells.

关 键 词：结直肠癌 成纤维细胞 上皮间质转化 活化 衰老 

分 类 号：R363.14[医药卫生—病理学]