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

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.