Experimental study on the inhibition of invasion and metastasis of oral cancer by the suppression of processing of E-cadherin

抑制E-cadherin加工抑制口腔癌侵袭和转移的实验研究

• 批准号: 17592083
• 负责人: HAYASHIDO Yasutaka
• 金额: $ 1.92万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592083/
• 关键词: oral cancer; invasion and metastasis; E-cadherin; processing; plasminogen; plasmin; cell aggregation; cell migration; アンチプラスミン

The participation of plasminogen activator/plasmin system in the expression and function of E-cadherin was examined in oral squamous cell carcinoma (SCC) cells. Treatment of SCC cells with plasminogen reduced the Ca^<2+>-dependent cell aggregation. SCC cells expressed E-cadherin at the cell membrane, and released a small amount of soluble E-cadherin at 80 kDa in the culture medium. Addition of plasminogen to SCC cells led to a decrease in the amount of E-cadherin of the cell membrane and the enhancement of the shedding of E-cadherin ectodomain. Plasmin directly cleaved E-cadherin of SCC cells and enhanced the motility of SCC cells. These results suggested that plasminogen activator/plasmin system might directly mediate the proteolytic processing of E-cadherin in oral SCC cells and that might facilitate the progression of oral SCC by downregulation of E-cadherin-mediated cell-cell adhesion.To examine the effect of downregulation of plasminogen activator/plasmin system by a2-antiplasmin (a2-AP) on cell-cell adhesion mediated by E-cadherin in oral SCC cells, the oral SCC cell line SCCKN was stably transfected with a2-AP cDNA. Induction of a2-AP expression led to the inhibition of the proteolysis of E-cadherin by plasminogen activator/plasmin in SCC cells, resulting in the enhancement of the cell aggregation and the suppression of the cell motility. Moreover, a2-AP also reduced the ability of SCC cells to invade type I collagen gel, and suppressed the tumorigenicity in vivo. These results suggested that downregulation of plasminogen activator/plasmin system by a2-AP might be a potent therapeutic approach to prevent the progression of oral SCC.

研究了纤溶酶原激活剂/纤溶酶系统在口腔鳞状细胞癌（SCC）中e -钙粘蛋白表达和功能中的作用。用纤溶酶原处理SCC细胞可减少Ca^<2+>依赖性细胞聚集。SCC细胞在细胞膜处表达E-cadherin，并在培养基中以80 kDa的速度释放少量可溶性E-cadherin。在SCC细胞中加入纤溶酶原导致细胞膜上e -钙粘蛋白的数量减少，e -钙粘蛋白外畴的脱落增强。纤溶蛋白直接裂解SCC细胞的e -钙粘蛋白，增强SCC细胞的运动性。这些结果提示，纤溶酶原激活剂/纤溶酶系统可能直接介导e -钙粘蛋白在口腔鳞状细胞中的蛋白水解过程，并可能通过下调e -钙粘蛋白介导的细胞-细胞粘连促进口腔鳞状细胞的进展。为了研究a2-antiplasmin （a2-AP）下调纤溶酶原激活剂/纤溶酶系统对E-cadherin介导的口腔SCC细胞-细胞粘附的影响，我们用a2-AP cDNA稳定转染口腔SCC细胞系SCCKN。诱导a2-AP表达可抑制SCC细胞中纤溶酶原激活剂/纤溶酶对E-cadherin的蛋白水解，导致细胞聚集增强，细胞运动性抑制。此外，a2-AP还能降低SCC细胞侵袭I型胶原凝胶的能力，抑制体内的致瘤性。这些结果表明，a2-AP下调纤溶酶原激活物/纤溶酶系统可能是预防口腔鳞状细胞癌进展的有效治疗方法。

项目成果

インテグリンβ8発現抑制が口腔扁平上皮癌細胞の増殖能と浸潤能に与える影響

抑制整合素β8表达对口腔鳞癌细胞增殖和侵袭能力的影响

• 发表时间: 2006
• 期刊: 口腔組織培養学会誌 15・1
• 作者: Hayashido;Y. et al.;Hayashido Y;北野尚孝
• 通讯作者: 北野尚孝

Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell cell adhesion.

α2-抗纤溶酶的诱导抑制由纤溶酶原激活剂/纤溶酶系统介导的E-钙粘蛋白加工，通过上调细胞粘附来抑制口腔鳞状细胞癌的进展。

• 发表时间: 2007
• 期刊: Oncol Rep. Feb;17(2)
• 作者: Hayashido Y;Hamana T;Ishida Y;Shintani T;Koizumi K;Okamoto T
• 通讯作者: Okamoto T

Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin.

• DOI: 10.3892/ijo.27.3.693
• 发表时间: 2005-09
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: Y. Hayashido;T. Hamana;Y. Yoshioka;H. Kitano;Koh-ichi Koizumi;T. Okamoto

Primary leiomyosarcoma of the mandible.

下颌原发性平滑肌肉瘤。

• DOI: 10.1016/s0196-0709(96)90077-0
• 发表时间: 1996
• 期刊: American journal of otolaryngology
• 影响因子: 2.5
• 作者: O. Laccourreye;R. Cauchois;Laurent Laccourreye;Didier Maurice;F. Carnot;Daniel Brasnu
• 通讯作者: Daniel Brasnu

言語聴覚士のための基礎知識 臨床歯科医学・口腔外科学

言语病理学家的基础知识：临床牙科/口腔外科

• 发表时间: 2016
• 作者: Masaki Honda;Taku Toriumi;本田雅規，秋田大輔，加野浩一郎，鶴町仁奈，鳥海 拓，井口慎也，鈴木大悟，河野英輔，松本太郎，磯川桂一郎.;磯川桂太郎，稲井哲一郎，入江一元，本田雅規 他13名;新井直也，新崎章，飯野光喜，本田雅規 他多数
• 通讯作者: 新井直也，新崎章，飯野光喜，本田雅規 他多数