Open AccessDual reporter genetic mouse models of pancreatic cancer identify an epithelial‐to‐mesenchymal transition‐independent metastasis program
Author(s) -
Chen Yang,
LeBleu Valerie S,
Carstens Julienne L,
Sugimoto Hikaru,
Zheng Xiaofeng,
Malasi Shruti,
Saur Dieter,
Kalluri Raghu
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809085
Subject(s) - epithelial–mesenchymal transition , metastasis , pancreatic cancer , cancer research , cancer , mesenchymal stem cell , cancer cell , biology , phenotype , adenocarcinoma , pathology , medicine , gene , genetics
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 α SMA ‐Cre and Fsp1‐Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma ( PDAC ) to monitor partial EMT program. Both α SMA ‐ 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 .