Journal
EMBO MOLECULAR MEDICINE
Volume 10, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201809085
Keywords
dual-recombinase system; metastasis; micrometastasis; pancreatic ductal adenocarcinoma; partial epithelial-to-mesenchymal transition
Categories
Funding
- NCI [P30CA16672, PO1CA117969]
- Cancer Prevention and Research Institute of Texas (CPRIT)
- CPRIT Award [RP150231]
- UT MDACC Khalifa Bin Zayed Al Nahya Foundation
- NIH [P30-CA016672, 5U24-CA126577]
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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 alpha SMA-Cre and Fsp1-Cre with genetically engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC) to monitor partial EMT program. Both alpha 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.
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