Dual reporter genetic mouse models of pancreatic cancer identify an epithelial-to-mesenchymal transition-independent metastasis program.
Dual reporter genetic mouse models of pancreatic cancer identify an epithelial-to-mesenchymal transition-independent metastasis program.
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DOI：
10.15252/emmm.201809085
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发表时间：
2018-10
影响因子：
11.1
通讯作者：
Kalluri R
中科院分区：
文献类型：
--
作者：
Chen Y;LeBleu VS;Carstens JL;Sugimoto H;Zheng X;Malasi S;Saur D;Kalluri R
上皮-间充质转化（EMT）是一种公认的真核细胞分化程序，也与侵袭性肿瘤相关。癌中的部分EMT程序赋予癌细胞间充质样特征，并被认为是转移所必需的。精确测定肿瘤中癌细胞部分EMT程序的频率及其在转移中的功能作用需要阐明。在这里，我们使用由αSMA‐Cre和Fsp 1 ‐Cre驱动的间充质细胞报告小鼠与发生自发性胰腺导管腺癌（PDAC）的基因工程小鼠来监测部分EMT程序。在原发性肿瘤中观察到αSMA-和Fsp 1-Cre-介导的部分EMT程序。已建立的转移主要由癌细胞组成，没有部分EMT程序的证据，如我们的命运映射方法所评估的。相反，表现出部分EMT程序的转移性癌细胞限于分离的单个癌细胞或微转移（3-5个癌细胞）。总的来说，我们的研究确定了保留上皮表型的大转移性结节，并可能揭示PDAC中的新转移程序。
Epithelial‐to‐mesenchymal transition (EMT) is a recognized eukaryotic cell differentiation program that is also observed in association with invasive tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal‐like features and is proposed as essential for metastasis. Precise determination of the frequency of partial EMT program in cancer cells in tumors and its functional role in metastases needs unraveling. Here, we employed mesenchymal cell reporter mice driven by αSMA‐Cre and Fsp1‐Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC) to monitor partial EMT program. Both αSMA‐ and Fsp1‐Cre‐mediated partial EMT programs were observed in the primary tumors. The established metastases were primarily composed of cancer cells without evidence for a partial EMT program, as assessed by our fate mapping approach. In contrast, metastatic cancer cells exhibiting a partial EMT program were restricted to isolated single cancer cells or micrometastases (3–5 cancer cells). Collectively, our studies identify large metastatic nodules with preserved epithelial phenotype and potentially unravel a novel metastasis program in PDAC.