整合素ανβ6-ERK2直接通路调控MMP-9分泌与结肠癌转移关系的实验研究  

Integrin ανβ6- ERK2 binding pathway mediates both MMP-9 secretion and metastasis of colon cancer cells

作　　者：杨广运[1] 徐克森[1] 张朝阳[1] 王金申[1] 王加勇[1] 刘炎锋[1] 帅晶[1] 寿楠海[1] 牛军[1] 

机构地区：[1]山东大擎齐鲁医院普外科山东大学肝胆血管外科研究所,济南250012

出　　处：《中华普通外科杂志》2007年第6期443-445,共3页Chinese Journal of General Surgery

基　　金：国家自然科学基金项目（30570833）;山东省自然科学基金项目（Y2005CA2）

摘　　要：目的 探讨在结肠癌细胞中整合素ανβ6-ERK2信号直接通路对MMP-9分泌的影响，进一步探讨结肠癌转移的机制。方法 采用流式细胞仪检测各细胞表面ανβ整合素的表达，采用明胶酶谱分析法和MMP-9活性检测法，定性定量分析不同结肠癌细胞在TCM中MMP-9的分泌水平。结果 WiDr MOCK，HT29MOCK细胞表面β6表达量明显高于WiDrA／Sense，HT29A／Sense细胞，且每个细胞分泌到无血清TCM中的MMP-9总量比WiDrA／Sense、HT29A／Sense细胞高2～3倍。SW480 β6 Full Length细胞分泌到TCM中的MMP-9分泌量不仅显著高于SW480MOCK细胞，而且能被MEK-1抑制剂PD98059所抑制。SW480 β6 Full Length细胞表面β6表达量和SW480 β6 Truncate细胞表面β6表达量相近，但SW480 β6 Truncate细胞在TCM中MMP-9的分泌量降低到SW480Mock细胞的分泌水平。结论 抑制β6的表达，阻滞MEK或删除β6-ERK2的连接位点均可抑制MMPO的分泌；阻断ανβ6-ERK2直接连接可降低结肠癌细胞MMPO的分泌，抑制结肠癌细胞侵袭和转移。Objective To investigate the effect of integrin ανβ6-associated ERK2 on both MMP-9 secretion and metastasis of colon cancer cells. Methods Flow cytometry was applied to analyse ανβ6 expression in colon cancer cell lines WiDr, HT29 and SW480. The MMP-9 levels in TCM were detected using Gelatin Zymography and MMP-9 activity assay. Results β6 expression on the cell surface of WiDr A/ Sense,HT29 A/Sense was significantly lower than that of WiDr MOCK, HT29 MOCK cells. Amounts of MMP-9 secreted per cell into serum-free TCM from both lines was 2 - 3-fold higher for WiDr MOCK, HT29 MOCK compared with WiDr A/Sense, HT29 A/Sense cells. SW480136 transfectants not only secrete markedly more MMP-9 into TCM than SW480 MOCK cells but this was inhibited by the MEK-1 inhibitor, PD98059. SW480 β6 Truncate cells lacking the binding site for ERK2 reduced MMP-9 secretion to levels seen for SW480 Mock cells. Conclusion Suppression of ανβ6 expression, MEK inhibition, or deletion of the ανβ6-ERK2 binding site inhibits MMP-9 secretion. Blockade of integrin ανβ6-ERK2 binding can inhibit MMP-9 secretion and inhibit cellullar metastases in colonic cancer.

关 键 词：结肠肿瘤 整合素类 基质金属蛋白酶类 肿瘤转移 肿瘤 实验性 

分 类 号：R686[医药卫生—骨科学]