Relationship between activation of TGF-β1 by αVβ8 integrin and the invasion and metastasis of colorectal cancer

αVβ8整合素激活TGF-β1与结直肠癌侵袭转移的关系

• 批准号: 16590271
• 负责人: KAWASHIMA Atsuhiro
• 金额: $ 1.15万
• 依托单位: National Hospital Organization Kanazawa Medical Center (Clinical Research Center)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590271/
• 关键词: Integrin; Colorectal cancer; TGF-β1; αVβ8; β-catenin; Invasion and metastasis

Relationship between the pattern of the expression of β-catenin and lymphatic metastasis in human colorectal cancers was examined. Paraffin-embedded sections and frozen sections of resected colorectal cancers were stained by antibodies for β-catenin, integrin α3β1, α5β1, β4, αVβ6, β8, TGF-β1, TGF receptor, and thrombospondin. The cases with the nuclear accumulation of β-catenin at the invasion front, showed more increased lymphatic metastases than the membranous or intracytoplasmic staining cases (p=0.0004). Moreover, β8-negative cases showed the more increasing clinical stages and lymphatic metastases. The expression of TGF-β1 and TGF receptor was synchronously observed in about 40% cases. Thrombospondin, which is known as one of activators of TGF-β1, was detected in only 7% cases. Unexpectedly, the expression of integrin β8 and TGF-β1 was not significantly correlated each other in immunohistochemical analyses. The expression of integrin αVβ6 also did not have any correlation with TGF-β1, TGF receptor or β-catenin. In conclusion, down regulation of αVβ8 was not the trigger of the activation of TGF-β1 inducing the accelerated metastatic ability in colorectal cancers.

探讨β-连环蛋白在结直肠癌中的表达模式与淋巴转移的关系。采用β-连环蛋白、整合素α3β1、α5β1、β4、αVβ6、β8、β1、转化生长因子受体和凝血酶反应蛋白对手术切除的结直肠癌石蜡切片和冰冻切片进行染色。侵袭前线β-连环蛋白核聚集者的淋巴转移率高于胞膜或胞浆染色者(p=0.0004)。此外，β-8阴性病例的临床分期和淋巴转移越多。约40%的病例同时表达转化生长因子-β-1和转化生长因子受体。作为转化生长因子-β-1激活剂之一的凝血酶原蛋白仅在7%的病例中被检测到。令人意外的是，在免疫组织化学分析中，整合素β8和转化生长因子β1的表达之间没有显著的相关性。整合素αVβ6的表达与转化生长因子-β1、转化生长因子受体、β-连环蛋白均无相关性。结论：αVβ8表达下调不是结直肠癌转化生长因子-β1激活导致肿瘤加速转移的触发因素。