Interaction of cancer cells with basement membrane proteins

癌细胞与基底膜蛋白的相互作用

• 批准号: 17014077
• 负责人: MIYAZAKI Kaoru
• 金额: $ 29.95万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17014077/
• 关键词: がん転移; 基底膜; 浸潤; ラミニン; MMP; がん浸潤; 転移; 細胞接着分子; 上皮-間葉変換(EMT); 細胞外マトリックス; がん; 浸潤・転移; 腫瘍増殖; プロテアーゼ; 阻害剤; マトリライシン; 細胞移動; ラミニン5; マトリプターゼ; 細胞接着

Tumor microenvironments play important roles in tumor progression. The present study demonstrated that the cell adhesion protein laminin-332 (Lm332 ; α3β3γ2) in the basement membrane was converted to a soluble factor capable of strongly promoting tumor cell migration by a proteolytic cleavage of its γ2 chain (Lmγ2). We previously showed that Lmγ2 is solely overexpressed when carcinoma cells invade into stroma. Here, we found that the Lmγ2 expression was induced by TGF-β or some other factors and promoted invasive growth of tumor cells in vivo. Furthermore, we found a novel vascular laminin, laminin-3B11, that was down-regulated in tumor vasculature. The matrix metalloproteinase matrilysin (MMP7) is frequently overexpressed in many types of human cancer and involved in tumor progression and metastasis. Our results suggested that MMP7 might enhance tumor metastasis by binding to cholesterol sulfate of cell membrane and then cleaving cell surface proteins and Lm332. Lmγ2 and MMP7 seem to be good targets for anti-cancer treatments.

肿瘤微环境在肿瘤进展中起重要作用。本研究表明，基底膜中的细胞粘附蛋白层粘连蛋白-332（Lm 332; α3β3γ2）通过其γ2链（Lmγ2）的蛋白水解裂解转化为能够强烈促进肿瘤细胞迁移的可溶性因子。我们以前的研究表明，当癌细胞侵入间质时，Lmγ2仅过表达。本研究发现Lmγ2的表达受TGF-β或其他因素的诱导，并促进肿瘤细胞的体内侵袭性生长。此外，我们发现了一种新的血管层粘连蛋白，层粘连蛋白-3B11，这是在肿瘤血管下调。基质金属蛋白酶基质溶解素（MMP 7）经常在许多类型的人类癌症中过表达，并参与肿瘤的进展和转移。我们的研究结果表明，MMP 7可能通过与细胞膜的胆固醇硫酸盐结合，然后切割细胞表面蛋白和Lm 332来促进肿瘤转移。Lmγ2和MMP 7似乎是抗癌治疗的良好靶点。

项目成果

N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3beta1 integrin-mediated cell migration.

• 发表时间: 2006
• 期刊: The Journal of biological chemistry
• 作者: Yanyang Zhao;T. Nakagawa;S. Itoh;K. Inamori;T. Isaji;Y. Kariya;A. Kondo;E. Miyoshi;K. Miyazaki-K.-Miyaza

Identification of amino acid residues of matrix metalloproteinase-2 essential for its selective inhibition by beta-amyloid precursor protein-derived inhibitor

基质金属蛋白酶 2 的氨基酸残基的鉴定对于 β-淀粉样前体蛋白衍生抑制剂的选择性抑制至关重要

• 发表时间: 2008
• 期刊: J Biol Chem 283
• 作者: Higashi;S. and Miyazaki;K
• 通讯作者: K

Identification of amino acid residues of matrix metalloproteinase-7 essential for binding to cholesterol sulfate

基质金属蛋白酶 7 与硫酸胆固醇结合所必需的氨基酸残基的鉴定

• 发表时间: 2008
• 期刊: J Biol Chem 838
• 作者: Higashi;S.;Oeda;M.;Yamamoto;K. and Miyazaki;K
• 通讯作者: K

癌の基底膜浸潤におけるEMT-細胞外マトリックス分子の作用

EMT-细胞外基质分子对肿瘤基底膜侵袭的影响

• 发表时间: 2008
• 期刊: 細胞工学 27
• 作者: 小川崇;宮崎香
• 通讯作者: 宮崎香

Identification of amino acid residues of matrix metallopro-teinase-2 essential for its selective inhibition by beta-amyloid precursor protein-derived inhibitor.

基质金属蛋白酶 2 的氨基酸残基的鉴定对于 β-淀粉样前体蛋白衍生抑制剂的选择性抑制至关重要。

• 发表时间: 2008
• 期刊: J Biol Chem. 283
• 作者: Higashi;S. Miyazaki;K.
• 通讯作者: K.