文章：

嗅介蛋白4导致结肠癌异型增生，但抑制其转移

Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer 

原文发布日期：2022-12-28 

英文摘要：

Development of colorectal cancer (CRC) is regulated by a series of genetic and microenvironmental alterations. Olfactomedin 4 (OLFM4) is a secreted glycoprotein that is highly expressed in the gastrointestinal tract and modulates inflammation. However, the role of OLFM4 in CRC is uncertain. Here we aimed to explore the function of OLFM4 in CRC in vivo and in vitro. The mRNA expression of OLFM4 was up-regulated in precursor lesions with dysplasia or ulcerative colitis but was reduced in CRC. OLFM4 neutralizing antibody suppressed inflammation-mediated early-stage CRC formation in an AOM/DSS colitis-associated cancer model. OLFM4 knockdown cells exhibited increased cell proliferation and motility in vitro and in vivo. Ablation of OLFM4 increased tumor growth and metastasis in xenograft experiments. In addition, OLFM4 knockdown cells showed elevated expression of colon cancer stem cell markers including CD133, resulting in increased metastasis via epithelial-mesenchymal transition signaling. This study demonstrated that OLFM4 regulates inflammation and cancer progression differently; ablation of OLFM4 promotes cancer metastasis via stemness and epithelial-mesenchymal transition. These results suggest a new route for controlling cancer progression and metastasis. 

摘要翻译：

结直肠癌（CRC）的发生发展受到一系列遗传学和微环境改变的调控。嗅素4（OLFM4）是一种在胃肠道高表达且参与炎症调节的分泌型糖蛋白，但其在CRC中的作用尚不明确。本研究旨在通过体内外实验探讨OLFM4在CRC中的功能。结果显示：OLFM4 mRNA在伴异型增生的癌前病变和溃疡性结肠炎组织中表达上调，但在CRC组织中表达降低；在AOM/DSS诱导的结肠炎相关癌症模型中，OLFM4中和抗体可抑制炎症介导的早期CRC形成；OLFM4敲除细胞在体内外均表现出增殖和迁移能力增强；异种移植实验表明OLFM4缺失会促进肿瘤生长和转移。此外，OLFM4敲除细胞中结肠癌干细胞标志物（包括CD133）表达升高，通过上皮-间质转化信号通路导致转移增强。本研究证实OLFM4以不同方式调控炎症和癌症进程：其缺失通过增强干性和上皮-间质转化促进癌症转移。这些发现为控制癌症进展和转移提供了新思路。

原文链接：

Olfactomedin 4 produces dysplasia but suppresses metastasis of colon cancer