NEW APPROACH TO DIGESTIVE ORGAN CANCER METASTASIS SUPPRESSION BY OSTEOPONTIN INHIBITION

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We performed exhaustive microarray analysis of HPC-3H4, with high potential for liver metastasis, in comparison with HPC-3, with low metastatic potential. The results indicated that OPN gene was up regulated (11.1-fold) in the highly liver metastatic cell line, and we hypothesized OPN as one of the novel candidate gene in pancreatic cancer metastasis.The metastatic rate of HPC-3 was 0% at 16 weeks after inoculation, and the metastatic rate of HPC-3H4 was 100% at 4 weeks. The metastatic rate of HPC-3opn, with transfection of OPN-expressing vector to HPC-3, was 0% at 16 weeks. Clear metastatic promotion was not found in the OPN forced expression cell line.The metastatic rate of HPC-3H4/miR-OPN, with transfection of OPN RNAi-expressing vector, was 25% (2/8) at 4 weeks and the metastases were mild and small in number. Thus, the effect of metastasis suppression was clearly observed after transfection of the RNAi expression vector. Moreover, an OPN-suppression test at the protein level was done by using an anti-OPN antibody. The metastatic rate of the control group was 100% (10/10) at 4 weeks. On the other hand, in the group given the anti-OPN antibody, half showed the effect of metastasis suppression.These results suggest that the anti-OPN Ab and OPN RNAi could be used for novel therapeutic strategies for inhibiting pancreatic cancer metastasis. Further studies to assess the clinical impact of the OPN-Ab in pancreatic cancer metastasis are needed.