Study of signal transduction of invasion / metastasis via PI3-kinase in the oral squamous cell carcinoma.

口腔鳞状细胞癌中PI3激酶侵袭/转移信号转导的研究。

• 批准号: 08672325
• 负责人: OKUMURA Kazuhiko
• 金额: $ 1.34万
• 依托单位: Health Sciences University of Hokkaido
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672325/
• 关键词: human OSCC cells; invasion; metastasis; PI3-kinase; FAK; tyrosine phosphorylation; Cell adhesiveness; Cell mitility; Rho family; 浸潤・転移; PI3-Kinase; Focal adhesion kinase

We established different invasiveness clones from human oral squamous cell carcinoma (OSCC) cell line SAS.The factor that defines the invasiveness of the two clones was also examined and two clones showed remarkably different cell motility. Here we report that analyzed signal transduction of cell motility in the OSCC.The role of phosphatidyinositol 3-kinase (PI3-kinase) activity in serum-stimulated tyrosine phosphorylation of focal adhesion kinase (p125^<FAK>) has been examined. The tyrosine phosdphorylation of p125^<FAK> of high-invasion clone SAS-H1, but not low-invasion clone SAS-L1 in response to serum was markedly inhibited by both wortmannin and LY294002, inhibitor of PI3-kinase in dose dependent manner. Furthermore, wortmannin inhibited adhesiveness to extracellular matrixs and cell motility.Serum-stimulated PI3-kinase activity, increased invasion of SAS-H1, but not SAS-L1 by endothelial cell monolayr assay.Thus, we have identified a PI3-kinase dependent signal transduction pathway in the cell motility of high-invasion OSCC cells, as SAS-H1, which leads to the phosphorylation of p125^<FAK>.

我们从口腔鳞状细胞癌(OSCC)细胞系SAS中建立了不同的侵袭性克隆，并对这两个克隆的侵袭性进行了检测，发现两个克隆的细胞运动能力有显著差异。在此，我们分析了口腔鳞状细胞癌细胞运动的信号转导。研究了磷脂酰肌醇3-激酶(PI3-K)活性在血清刺激的粘着斑激酶(p125^&lt；FAK&gt；)酪氨酸磷酸化中的作用。高侵袭性克隆SAS-H1的p125^-lt；FAK&gt；而低侵袭性克隆SAS-L1对血清的酪氨酸磷酸化反应可被Wortmannin和PI3-Kinase抑制剂LY294002明显抑制，且呈剂量依赖关系。此外，Wortmannin抑制细胞外基质的黏附和细胞运动。血清刺激PI3-激酶活性，增加SAS-H1的侵袭力，但内皮细胞单层分析不增加SAS-L1。因此，我们确定在高侵袭性口腔鳞癌细胞的细胞运动中有一条依赖PI3-激酶的信号转导通路，即SAS-H1，导致p125^&lt；FAK&gt；

项目成果

Shibata, T.: "Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation,but not growth." Tumor Biol. 17. 168-175 (1996)

Shibata, T.：“表皮生长因子对人鳞状细胞癌运动和基质降解的增强作用，但对生长没有作用。”

Abiko, Y.: "Basaloid-squamous cell carcinoma of the floor of the mouth:characterization of a cell line." J.Oral Pathol.Med.26. 367-370 (1997)

Abiko, Y.：“口底基底样鳞状细胞癌：细胞系的特征。”

奥村 一彦: "舌扁平上皮癌細胞の浸潤シグナルにおよぼすWortmanninの影響" 口腔組織培養研究会誌. 4. 121-122 (1996)

Kazuhiko Okumura：“Wortmannin 对舌鳞状细胞癌细胞侵袭信号的影响”口腔组织培养研究会杂志 4. 121-122 (1996)。

北所 弘之: "Hepatocyte growth factorによる口腔扁平上皮癌細胞の浸潤シグナルの検討" 口腔組織培養研究会誌. 4. 123-124 (1996)

Hiroyuki Kitasho：“通过肝细胞生长因子检查口腔鳞状细胞癌细胞的侵袭信号”口腔组织培养研究会杂志4. 123-124（1996）。

Shibata, T., et al.: "Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation, but not growth." Tumor Biol. 17. 168-175 (1996)

Shibata, T. 等人：“增强表皮生长因子对人鳞状细胞癌运动和基质降解的影响，但对生长没有影响。”