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

研究结直肠癌组织中β-catenin的表达与淋巴结转移的关系。用β-连环蛋白、整合素α3β1、α5β1、β4、αVβ6、β8、TGF-β1、TGF受体和血小板反应蛋白的抗体对切除的结直肠癌的石蜡包埋切片和冷冻切片进行染色。β-连环蛋白在浸润前沿的核积聚的病例比膜或胞浆内染色的病例显示更多的淋巴转移（p=0.0004）。β8阴性者临床分期及淋巴结转移明显增加。TGF-β1和TGF-受体的表达在40%左右呈同步性。血小板反应蛋白是TGF-β1的激活剂之一，仅在7%的病例中检测到。出乎意料的是，在免疫组化分析中整合素β8和TGF-β1的表达彼此没有显著相关性。整合素αVβ6的表达与TGF-β1、TGF受体及β-catenin均无相关性。结论：αVβ8的下调不是TGF-β1激活诱导结直肠癌转移能力增强的触发因素。

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.