Mechanisms ofpromoting the bone invasion of cancer cells by osteopontin

骨桥蛋白促进癌细胞骨侵袭的机制

• 批准号: 18592190
• 负责人: HIGUCHI Yasunori
• 金额: $ 2.57万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592190/
• 关键词: metastasis; osteopontin; trans genic mouse; invasion of cancer cells; melanoma; synthetic peptide; リコンビナント蛋白; ペプチド

We isolated the mouse osteopontin(OPN) gene and analyzed its structure and function. Furthermore, we generated transgenic(TG) mice expressing OPN under the control of the α1-anti-trypsin promoter. OPN contains a GRGDS integrin-binding domain and is shown to promote the adhesion and migration of cancer cells. Osteoclasts have been shown to bind to bone matrix via αvβ3 and bone sialoprotein for attachment.We analyzed the role of OPN under the infiltration and metastasis of cancer cells in vivo and in vitro. As a result1. Bone infiltration and lung metastasis of cancer cellsOPN-TG mice and wild-type mice were given subcutaneous or intra-gingival injections of B16 melanoma cells. There was no significant difference of tumor growth and invasion between two groups of mice. Unexpectedly, significant inhibition of lung metastases in OPN-TG mice was observed as compared with the wild-type mice. The iv. pre-administration of recombinant OPN significantly inhibited the lung metastases with melanoma cells. 2. Construction of recombinant proteins and synthetic peptides possessing a functional domain derived from OPN2. Construction of recombinant proteins and synthetic peptides possessing a functional domain derived from OPNTo construct a recombinant proteins, the GST-fusion DNAs encoding the putative functional fragments were made and transfected into E. coli. But, no production of protein was confirmed. We therefore made some peptides with or without an Arg-Gly-Asp sequence. In preliminary experiment, a significant reduction in the number of lung tumor colonies was observed at a peptide containing Arg-Gly-Asp sequence.

我们分离了小鼠骨桥蛋白（OPN）基因，并分析了其结构和功能。此外，我们在α1-抗trypsin启动子的控制下产生了表达OPN的转基因（TG）小鼠。 OPN包含一个GRGDS整联蛋白结合结构域，并显示出促进癌细胞的粘合剂和迁移。破骨细胞已显示出通过αVβ3和骨唾液蛋白与骨基质结合的附着。结果1。对癌细胞OPN-TG小鼠和野生型小鼠的骨浸润和肺转移，对B16黑色素瘤细胞的皮下或内注射注射。两组小鼠之间的肿瘤生长和侵袭没有显着差异。出乎意料的是，与野生型小鼠相比，观察到OPN-TG小鼠中肺转移的显着抑制作用。 iv。重组OPN的预热前给药可显着抑制黑色素瘤细胞的肺转移。 2。具有源自OPN2的功能域的重组蛋白和合成肽的结构。重组蛋白和具有源自OPN的功能结构域的合成肽的构建，制造了重组蛋白，制造了编码假定功能片段的GST融合DNA，并将其翻译成大肠杆菌。但是，没有确认蛋白质的产生。因此，我们制作了有或没有Arg-Gly-Asp序列的一些胡椒粉。在初步实验中，在含有arg-gly-asp序列的肽处观察到肺肿瘤菌落数量的显着减少。

项目成果

Elevated soluble ADAM8 in BALF in patients with eosinophilic pneumonia.

嗜酸性粒细胞性肺炎患者 BALF 中可溶性 ADAM8 升高。

• 发表时间: 2007
• 期刊: International Archives of Allergy and Immunology 142
• 作者: Matsuno O.;Miyazaki E.;Nureki S.;Ueno T.;Ando M..;Ito K..;Kumamoto T. and Higuchi Y.
• 通讯作者: Kumamoto T. and Higuchi Y.

健康と病気の仕組みが分かる「解剖生理学」

解剖学和生理学：了解健康和疾病的机制

• 发表时间: 2008
• 作者: Matsuno O.;Miyazaki E.;Nureki S.;Ueno T.;Ando M..;Ito K..;Kumamoto T. and Higuchi Y.;アン・ウオー/アリソン・グラント
• 通讯作者: アン・ウオー/アリソン・グラント