Integrin alphavbeta6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver
Integrin alphavbeta6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver
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整合素αvβ6介导结肠癌细胞在肝脏定植和转移的潜力
DOI：
10.1111/j.1349-7006.2008.00762.x
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发表时间：
2008-05-01
期刊：
影响因子：
5.7
通讯作者：
Niu, Jun
中科院分区：
文献类型：
--
作者：
Yang, Guang-Yun;Xu, Ke-Sen;Niu, Jun
整合素α v β 6（α v β 6）与结肠癌进展相关。为了检测α v β 6对肝转移的影响，通过免疫沉淀法检测α v β 6对单克隆抗体（mAb）2G 2的特异性。本文检测了63例肝转移癌和358例结肠癌组织中整合素α v β 6免疫反应性（IR）。结果表明，单抗2G 2特异性识别α v β 6，肝转移癌组织中α v β 6的阳性率（71.4%，45/63）高于原发性结肠癌组织（34.0%，122/358）（P < 0.01）。α v β 6阳性组肝转移率（17%，21/122）高于α v β 6阴性组（3%，7/236）（P < 0.01）。为了检查与α v β 6调节肝中结肠转移相关的潜在机制，在裸鼠中进行实验性肝转移（HT 29转染子的脾内注射）和肝定殖测定（WiDr转染子直接注射到肝中）;这些证明α v β 6有助于促进肝中癌细胞的转移潜力和存活。用Biotrak MMP-9活性测定系统和明胶酶谱法检测HT 29和WiDr细胞培养液中MMP-9的水平，结果表明抑制α v β 6-IR可抑制MMP-9的活性和分泌。Transwell迁移实验也显示α v β 6对HT 29/WiDr mock和HT 29/WiDr反义β 6细胞在纤连蛋白上的迁移有促进作用（P < 0.01）。我们的结论是，α v β 6可能介导结肠癌细胞在肝脏定植和转移的潜力。α v β 6可能参与的机制包括促进MMP-9分泌、增强纤连蛋白上的迁移和肝中癌细胞的存活。
Integrin alphavbeta6 (alpha v beta 6) is correlated with colon cancer progression. To detect the effects of alpha v beta 6 on liver metastasis, the specificity of alpha v beta 6 against the monoclonal antibody (mAb) 2G2 was examined by immunoprecipitation. Integrin alpha v beta 6-immunoreactivity (IR) in liver metastasis tissues (63 cases) and colon carcinoma (358 cases) were examined. These results showed that alpha v beta 6 was specifically recognized by the mAb 2G2, and that rates of alpha v beta 6 positivity in liver metastatic tissues (71.4%, 45/63) were higher than that for primary colon cancer (34.0%, 122/358) (P < 0.01). Patients who were alpha v beta 6-positive had higher liver metastasis rates (17%, 21/122) than those who were alpha v beta 6-negative (only 3%, 7/236) (P < 0.01). To examine the underlying mechanisms associated with alpha v beta 6 regulating colonic metastasis in the liver, experimental liver metastasis (intrasplenic injection of HT29 transfectants) and liver colonization assays (direct injection of WiDr transfectants into the liver) in nude mice were performed; these demonstrated that alpha v beta 6 contributed to the promotion of the metastatic potential and the survival of cancer cells in the liver. Matrix metalloproteinase-9 (MMP-9) levels in the cultures of both HT29 and WiDr cells were detected by the Biotrak MMP-9 activity assay system and gelatin zymography assay, and showed that suppression of alpha v beta 6-IR inhibited MMP-9 activity and secretion. Transwell migration assay in vitro also showed that alpha v beta 6 promoted migration on fibronectin for HT29/WiDr mock compared with HT29/WiDr antisense beta 6 transfects (P < 0.01). We concluded that alpha v beta 6 may mediate the potential for colon cancer cells to colonize in and metastasize to the liver. The mechanisms that alpha v beta 6 may be involved in include the promotion of MMP-9 secretion, the enhancement of migration on fibronectin, and the survival of cancer cells in the liver.