Establishment of invasion/metastasis inhibition therapy against oral squamous cell carcinomas : a basic study.

针对口腔鳞状细胞癌的侵袭/转移抑制疗法的建立：一项基础研究。

• 批准号: 20592205
• 负责人: KAWANO Kenji
• 金额: $ 2.5万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20592205/
• 关键词: 口腔扁平上皮癌; 浸潤; 転移; 接着分子; アノイキス; anoikis; 口腔扁平上癌

Multicellular aggregates of MOK205, an oral squamous carcinoma cell line, transformed to monolayer colonies on laminin 5 and type 1 collagen substrates, and then showed cell dispersion only on laminin 5. This phenomenon was triggered by the increased motility and disruption of E-cadherin-mediated intercellular adhesion via the activation of integrin receptor by laminin 5. When PP1, a specific inhibitor of the Src family, was added to the cell scattering model of MOK205, cell dispersion was almost completely blocked, suggesting that Src was involved in the interaction between integrin and cadherin. In addition, fluorescence microscopic observation revealed that phospho-tyrosine 215-Src and phospho-tyrosine 529-Src were localized along the cell membrane of the intercellular adhesion of MOK205 immediately before cells started dispersion on laminin 5. Taken together, these results suggested that Src could be a target of the invasion/metastasis inhibition therapy against oral squamous cell carcinomas.

MOK 205是一种口腔鳞状细胞癌细胞系，其多细胞聚集体在层粘连蛋白5和1型胶原基质上转化为单层集落，然后仅在层粘连蛋白5上显示细胞分散。这一现象是由层粘连蛋白5激活整合素受体引起的E-钙粘蛋白介导的细胞间粘附的运动性增加和破坏引发的。当PP 1，Src家族的特异性抑制剂，被添加到MOK 205的细胞分散模型，细胞分散几乎被完全阻断，这表明Src参与整合素和钙粘蛋白之间的相互作用。此外，荧光显微镜观察显示，在细胞开始分散在层粘连蛋白5上之前，磷酸酪氨酸215-Src和磷酸酪氨酸529-Src沿着MOK 205的细胞间粘附的细胞膜定位。综上所述，这些结果表明Src可能是针对口腔鳞状细胞癌的侵袭/转移抑制治疗的靶点。