Angiopoietin-like Protein 2 Is an Important Facilitator of Inflammatory Carcinogenesis and Metastasis
Angiopoietin-like Protein 2 Is an Important Facilitator of Inflammatory Carcinogenesis and Metastasis
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DOI：
10.1158/0008-5472.can-11-1758
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Oike, Yuichi
中科院分区：
文献类型：
--
作者：
Aoi, Jun;Endo, Motoyoshi;Oike, Yuichi
慢性炎症在癌症发展的不同阶段起着重要作用，包括癌发生、肿瘤侵袭和转移，但将炎症与癌症发展联系起来的分子机制尚未完全阐明。在这里，我们报告，血管生成素样蛋白2（Angptl2），最近被确定为慢性炎症介质的表达，是高度相关的化学诱导的皮肤鳞状细胞癌（SCC）小鼠模型中的癌变频率。此外，Angptl2在SCC中的表达与肿瘤细胞转移到远处次级器官和淋巴结的频率高度相关。当在皮肤上皮细胞中表达Angptl2的转基因小鼠中诱导SCC时，与野生型小鼠相比，SCC中的上皮向间充质转化以及肿瘤血管生成和淋巴管生成显著增加，导致肿瘤细胞转移增加和生存期缩短。相反，在化学诱导的SCC小鼠模型中，Angptl2敲除小鼠中的癌发生和转移显著减弱，导致与野生型小鼠相比延长的存活期。总之，我们认为Angptl2有助于增加癌发生和转移，
Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis, but molecular mechanisms linking inflammation to cancer development have not been fully clarified. Here, we report that expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, Angptl2 expression in SCC is highly correlated with the frequency of tumor cell metastasis to distant secondary organs and lymph nodes. When SCC was induced in transgenic mice expressing Angptl2 in skin epithelial cells, epithelial-to-mesenchymal transitions in SCC as well as tumor angiogenesis and lymphangiogenesis were significantly increased, resulting in increased tumor cell metastasis and shortened survival compared with wild-type mice. Conversely, in a chemically induced SCC mouse model, carcinogenesis and metastasis were markedly attenuated in Angptl2 knockout mice, resulting in extended survival compared with wild-type mice. Overall, we propose that Angptl2 contributes to increased carcinogenesis and metastasis