骨桥蛋白抑制可减少在小鼠模型中注入脾脏的人胰腺癌细胞异种移植的肝转移。

Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model.

机构信息

Department of Surgery, Sapporo Medical University School of Medicine, S1W17, Chuo-ku, Sapporo, 060-8556, Japan.

出版信息

Surg Today. 2010 Apr;40(4):347-56. doi: 10.1007/s00595-009-4082-x. Epub 2010 Mar 26.

DOI:10.1007/s00595-009-4082-x

PMID:20339989

Abstract

PURPOSE

Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of liver metastasis. This study evaluated the possibility that osteopontin (OPN) RNA interference (RNAi) and anti-OPN antibody (Ab) could have antimetastatic effects.

METHODS

The differential gene expression was measured in a parental cell line, HPC-3, and an established highly liver metastatic cell line, HPC-3H4. This study investigated the effect of OPN RNAi and anti-OPN Ab on the metastatic ability of HPC-3H4 to the liver. An OPN RNAi-expressing vector was introduced into HPC-3H4 cells (HPC-3H4/miOPN), in which OPN production was reduced to the level of the parental HPC-3 cells. Finally, the ability of anti-OPN Ab to suppress liver metastasis was investigated.

RESULTS

Osteopontin was upregulated 11.1-fold in HPC-3H4 in comparison to HPC-3. The metastatic rate of HPC-3H4/miOPN was significantly reduced to 25% in comparison to the 100% metastatic rate of HPC-3H4 and control HPC-3H4/miNeg cells (P < 0.01). The metastatic rate of the group given anti-OPN Ab was 50%.

CONCLUSION

OPN RNAi and anti-OPN Ab had remarkable inhibitory effects against liver metastasis by the pancreatic cancer cell line.

摘要

目的

由于胰腺癌肝转移发生率高，其预后是所有消化道恶性肿瘤中最差的。本研究评估了骨桥蛋白（OPN）RNA 干扰（RNAi）和抗 OPN 抗体（Ab）是否具有抗转移作用。

方法

在亲本细胞系 HPC-3 和已建立的高肝转移细胞系 HPC-3H4 中测量差异基因表达。本研究探讨了 OPN RNAi 和抗 OPN Ab 对 HPC-3H4 向肝脏转移能力的影响。将 OPN RNAi 表达载体引入 HPC-3H4 细胞（HPC-3H4/miOPN），其中 OPN 产生降低至亲本 HPC-3 细胞的水平。最后，研究了抗 OPN Ab 抑制肝转移的能力。