NEW APPROACH TO DIGESTIVE ORGAN CANCER METASTASIS SUPPRESSION BY OSTEOPONTIN INHIBITION
| 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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Report
(4 results)
Research Products
(8 results)
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[Journal Article] The Establishment of The Bank of High Metastatic Cell Lines of Human Digestive and Breast Cancer2005
Author(s)
Keisuke OHNO, Takahiro YASOSHIMA, Hidefumi NISHIMORI, Fumitake HATA, Rika FUKUI, Yoshiyuki YANAI, Kenjiro KAMIGUCHI, Ryuichi DENNO, Takayuki SHISHIDO, Itaru HIRAI, Hiroeki SAHARA, Nobuaki TAKAHASHI, Yasuo KOKAI, Noriyuki SATO, Koichi HIRATA.
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Journal Title
Bulletin of the Marine Biomedical Institute, Sapporo Medical University School of Medicine. 6
Pages: 35-39
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Metastatic-Associated Biological properties and differential gene expression profiles in established highly liver or peritoneal metastatic cell lines of human pancreatic cancer2004
Author(s)
K.Ohno, F.Hata, H.Nishimori, T.Yasoshima, Y.Yanai, K.Sogahata, E.Ezoe, H.Tanaka, K.Kamiguchi, H.Isomura, R.Denno, N.Sato, K.Hirata.
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Journal Title
J.Exp.Clin.Can.Res. 22
Pages: 623-631
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Profiling Analysis of Differential Gene Expression Between Hematogenous and Peritoneal Metastatic Sublines of Human Pancreatic Cancer Using DNA chip2004
Author(s)
F.Hata, H.Nishimori, T.Yasoshima, H.Tanaka, K.Ohno, Y.Yanai, E.Ezoe, K.Kamiguchi, H.Isomura, R.Denno, N.Sato, K.Hirata.
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Journal Title
J.Exp.Clin.Cancer Res. 23
Pages: 5113-520
Description
「研究成果報告書概要(欧文)」より
Related Report
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