| Project/Area Number |
16591334
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
HATA Fumitake SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (70291557)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Koichi SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50136959)
傳野 隆一 札幌医科大学, 保健医療学部, 教授 (40163943)
西森 英史 札幌医科大学, 医学部, 助手 (70336402)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Osteopontin / liver metasitasis / pancreatic cancer / animal metastatic model / gene expression / gene transfection / 遺伝子導入 / RNAi / osteoponitn |
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| Research Abstract |
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.
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