Slug expression enhances tumor formation in a noninvasive rectal cancer model.
Slug expression enhances tumor formation in a noninvasive rectal cancer model.
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DOI：
10.1016/j.jss.2011.02.012
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Watson DK
中科院分区：
文献类型：
--
作者：
Camp ER;Findlay VJ;Vaena SG;Walsh J;Lewin DN;Turner DP;Watson DK
上皮-间充质转化（EMT）是一系列分子变化，允许上皮癌细胞获得间充质细胞的特性：增加的运动性和侵袭性以及保护免于凋亡。转录调节因子如Slug介导EMT，部分抑制E-钙粘蛋白转录。我们报告了一种新的，非侵入性的体内直肠癌模型，以探讨Slug在结直肠癌（CRC）肿瘤发展中的作用。为了产生过表达Slug的DLD-1细胞（Slug DLD-1），使用Slug或空（空DLD-1）pCMV-3 Tag-1（卡那霉素抗性）载体进行转染。评价细胞的Slug和E-钙粘蛋白表达以及细胞迁移和侵袭。对于体内研究，使用内窥镜引导将结肠癌细胞（亲代DLD-1、Slug DLD-1、空DLD-1和HCT-116）粘膜下注射到裸小鼠的直肠后壁。28天后，收获肿瘤并分析组织。在我们的结肠癌细胞系组中，Slug表达与E-钙粘蛋白表达和增强的迁移/侵袭呈负相关。Slug DLD-1细胞显示与空DLD-1相比，Slug表达增加21倍，E-cadherin表达降低19倍。类似地，Slug DLD-1细胞具有显著增强的细胞迁移和侵袭。在原位直肠癌模型中，Slug DLD-1细胞在9/10（90%）的小鼠（平均体积= 458 mm 3）中形成直肠肿瘤，而空DLD-1细胞仅为1/10（10%）。蛞蝓介导EMT，增强体内直肠肿瘤形成。我们的非侵入性体内模型使研究人员能够探索临床相关直肠癌中基因改变的分子后果，以努力为直肠癌患者开发新的治疗方法。
Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility and invasion and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, non-invasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 days, tumors were harvested and tissue was analyzed. Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm3) compared with only 1/10 (10%) with empty DLD-1 cells. Slug mediates EMT with enhanced in vivo rectal tumor formation. Our non-invasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer.
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影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
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