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，并对其结构和功能进行了分析。此外，我们产生了在α1-抗胰蛋白酶启动子控制下表达OPN的转基因（TG）小鼠。OPN含有GRGDS整合素结合结构域，并显示促进癌细胞的粘附和迁移。破骨细胞可通过αvβ3和骨唾液酸蛋白与骨基质结合粘附，我们分析了骨桥蛋白在体内、外肿瘤细胞浸润和转移中的作用。结果1。肿瘤细胞的骨浸润和肺转移OPN-TG小鼠和野生型小鼠皮下或牙龈内注射B16黑色素瘤细胞。两组小鼠的肿瘤生长和侵袭能力无明显差异。出乎意料的是，与野生型小鼠相比，在OPN-TG小鼠中观察到肺转移的显著抑制。IV。预先给予重组OPN显著抑制黑色素瘤细胞的肺转移。2.具有源自OPN 2的功能结构域的重组蛋白和合成肽的构建。具有OPN功能域的重组蛋白和合成肽的构建为了构建重组蛋白，制备编码推定功能片段的GST融合DNA并转染E.杆菌但是，没有蛋白质的生产被证实。因此，我们制备了一些具有或不具有Arg-Gly-Asp序列的肽。在初步实验中，在含有Arg-Gly-Asp序列的肽处观察到肺肿瘤集落数量的显著减少。

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