Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4802
Peer-review started: April 14, 2020
First decision: June 18, 2020
Revised: July 1, 2020
Accepted: August 4, 2020
Article in press: August 4, 2020
Published online: August 28, 2020
Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer (PC). There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling.
To create a new xenograft animal model that can faithfully recapitulate the features of human PC.
Interleukin 2 receptor subunit gamma (IL2RG) gene knockout Syrian hamster was created and characterized. A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically. Tumor growth, local invasion, remote organ metastasis, histopathology, and molecular alterations of tumor cells and stroma were compared over time.
The Syrian hamster with IL2RG gene knockout (named ZZU001) demonstrated an immune-deficient phenotype and function. ZZU001 hamsters faithfully recapitulated most features of human PC, in particular, they developed metastasis at multiple sites. PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes, whereas PC tissues derived from immune-deficient mice did not present such features.
ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice. ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.
Core tip: Xenograft cell transplantation into immune-deficient mice has become the gold standard for assessing tumor progression and efficacy of cancer drugs. However, xenografting human pancreatic cancer (PC) models in nude mice rarely results in development of metastasis and thus does not accurately reflect tumor progression as seen in the human disease. Here, we created a new immune-deficient Syrian hamster with interleukin 2 receptor subunit gamma (IL2RG) gene knockout and demonstrated that the IL2RG-/- Syrian hamster is a promising animal model that can faithfully recapitulate most features of human PC, notably multiple sites of metastasis. Furthermore, this model can present other key features of human PC, such as stromal reaction and the communication between stromal cells and PC cells.