乙酰肝素酶-1/多配体蛋白聚糖-1轴对肝癌细胞侵袭能力的影响

乙酰肝素酶-1(Heparanase-1,HPA-1)/多配体蛋白聚糖-1(Syndecan-1,SDC-1)轴调控多种肿瘤细胞的转移。肿瘤细胞侵袭能力的改变是导致肿瘤脱离原发组织,进而向远隔器官转移的关键启动因素。为了检测Heparanase-1/Syndecan-1轴在肝癌细胞中是否存在及其对肝癌细胞侵袭能力的影响,我们利用SDC-1小干扰RNA及重组HPA-1(rHPA-1)分别处理肝癌细胞Hepa1-6,再通过反转录PCR(RT-PCR)、Western-blot及免疫细胞化学检测SDC-1表达,应用体外基质胶侵袭实验观察细胞侵袭能力的改变。结果显示:SDC-1小干扰RNA明显抑制SDC-1表达;r HPA-1处理显著下调SDC-1蛋白的分子量,但没有改变SDC-1的mRNA表达;SDC-1表达下调及rHPA-1处理均促进Hepa1-6细胞的侵袭。因此得出结论:HPA-1通过作用于SDC-1蛋白,即形成Heparanase-1/Syndecan-1轴启动肝癌细胞转移。

Effects of Heparanase-1/Syndecan-1 Axis on Invasive Ability of Hepatocarcinoma Cell

Heparanase- 1 / Syndecan- 1 axis mediates the metastasis of many types of tumors. The change in invasive ability of tumor cell is the key factor to induce the spread of tumor cells from primary lesions to distant sites. This study aims to detect the existence of Heparanase- 1 / syndecan- 1 axis and the involved effects of Heparanase- 1 / syndecan- 1 axis on invasive ability of hepatocarcinoma cell Hepa1- 6. SDC- 1 small interfering RNA and recombinant HPA- 1( rHPA- 1) were used to treat Hepa1- 6 cells,and then SDC- 1 expression was detected by RT- PCR,Western- blot and immunocytochemistry assays,and Matrigel invasion test was performed to observe the invasive ability. The results showed that SDC- 1 small interfering RNA obviously inhibited SDC- 1expression; the treatment of rHPA- 1 significantly down- regulated the molecule weight of SDC- 1,but not changed the levels of SDC- 1 mRNA; both SDC- 1 knockdown and r HPA- 1 treatment promoted the invasion of Hepa1- 6 cells. In conclusion,HPA- 1 induces the metastasis of hepatocarcinoma cell via acting on SDC- 1 protein.