NEW APPROACH TO DIGESTIVE ORGAN CANCER METASTASIS SUPPRESSION BY OSTEOPONTIN INHIBITION

通过骨桥蛋白抑制抑制消化器官癌转移的新方法

• 批准号: 16591334
• 负责人: HATA Fumitake
• 金额: $ 2.24万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591334/
• 关键词: Osteopontin; liver metasitasis; pancreatic cancer; animal metastatic model; gene expression; gene transfection; 遺伝子導入; RNAi; osteoponitn

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.

我们对具有较高肝转移潜力的 HPC-3H4 进行了详尽的微阵列分析，而与具有较低转移潜力的 HPC-3 相比。结果表明，OPN基因在高肝转移细胞系中表达上调（11.1倍），我们推测OPN是胰腺癌转移的新候选基因之一。接种后16周HPC-3的转移率为0%，接种4周后HPC-3H4的转移率为100%。将OPN表达载体转染至HPC-3后，16周时HPC-3opn的转移率为0%。 OPN强制表达细胞系未发现明显的转移促进作用。转染OPN RNAi表达载体的HPC-3H4/miR-OPN在4周时的转移率为25%（2/8），且转移轻微且数量少。因此，在转染RNAi表达载体后，可以清楚地观察到转移抑制的效果。此外，使用抗OPN抗体进行了蛋白质水平的OPN抑制试验。对照组4周时转移率为100%（10/10）。另一方面，在给予抗OPN抗体的组中，一半显示出抑制转移的效果。这些结果表明，抗OPN Ab和OPN RNAi可用于抑制胰腺癌转移的新治疗策略。需要进一步研究来评估 OPN-Ab 对胰腺癌转移的临床影响。

项目成果

ヒト消化器癌および乳癌の転移株細胞バンクの樹立

人胃肠癌及乳腺癌转移细胞库的建立

• 发表时间: 2005
• 期刊: 札医大臨海医学紀要 6
• 作者: 大野敬祐;八十島孝博;西森英史;秦 史壮;他
• 通讯作者: 他

Metastatic-Associated Biological properties and differential gene expression profiles in established highly liver or peritoneal metastatic cell lines of human pancreatic cancer

已建立的高度肝或腹膜转移的人胰腺癌细胞系的转移相关生物学特性和差异基因表达谱

• 发表时间: 2004
• 期刊: J.Exp.Clin.Can.Res. 22
• 作者: 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.
• 通讯作者: K.Hirata.

Biological properties and differential gene expression profiles in established highly liver or peritoneal metastatic cell lines of human pancreatic cancer.

已建立的高度肝或腹膜转移的人胰腺癌细胞系的生物学特性和差异基因表达谱。

• 发表时间: 2004
• 期刊: J. Clin. Exp. Can. Res. 22
• 作者: Ohno K;Hata F;Nishimori H;et al.
• 通讯作者: et al.

Profiling Analysis of Differential Gene Expression Between Hematogenous and Peritoneal Metastatic Sublines of Human Pancreatic Cancer Using DNA chip

利用 DNA 芯片对人胰腺癌血行和腹膜转移亚系之间的差异基因表达进行谱分析

• 发表时间: 2004
• 期刊: J.Exp.Clin.Cancer Res. 23
• 作者: F.Hata;H.Nishimori;T.Yasoshima;H.Tanaka;K.Ohno;Y.Yanai;E.Ezoe;K.Kamiguchi;H.Isomura;R.Denno;N.Sato;K.Hirata.
• 通讯作者: K.Hirata.

The Establishment of The Bank of High Metastatic Cell Lines of Human Digestive and Breast Cancer

人类消化道癌和乳腺癌高转移细胞系库的建立

• 发表时间: 2005
• 期刊: Bulletin of the Marine Biomedical Institute, Sapporo Medical University School of Medicine. 6
• 作者: 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.
• 通讯作者: Koichi HIRATA.