Author:
Liu Zhenyang,Ahn Michael Ho-Young,Kurokawa Tomohiro,Ly Amy,Zhang Gong,Wang Fuyou,Yamada Teppei,Sadagopan Ananthan,Cheng Jane,Ferrone Cristina R.,Liss Andrew S.,Honselmann Kim C.,Wojtkiewicz Gregory R.,Ferrone Soldano,Wang Xinhui
Abstract
Abstract
Background
Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice.
Methods
We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10–20 mm in diameter, we performed survival surgery on each mouse to harvest 90–95% of subcutaneous PDX (incomplete resection), allowing the remaining 5–10% of PDX to continue growing in the same mouse.
Results
We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors.
Conclusions
Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.
Funder
National Cancer Institute
Massachusetts General Hospital
National Institute of Dental and Craniofacial Research
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
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