期刊
INTERNATIONAL JOURNAL OF CANCER
卷 140, 期 6, 页码 1356-1363出版社
WILEY
DOI: 10.1002/ijc.30561
关键词
patient-derived xenograft; lymphoproliferation; colorectal cancer; pancreatic cancer
类别
资金
- Deutsche Forschungsgemeinschaft (DFG) [KFO 227/GL286/1-1, KFO 227/BA 4806/1-2, SFB873]
- Baden-Wuerttemberg Stiftung gGmbH [P-LS-ASII/33]
- Helmholtz Association [iMed]
- EU Framework Programme Horizon2020 (TRANSCAN-2 ERA-NET) [TACTIC]
- German Cancer Aid [Colon-Resist-Net (SP2, SP4)]
- DKFZ-Heidelberg Center for Personalized Oncology (DKFZ-HIPO) [HIPO-002, HIPO-012]
- National Center for Tumor Diseases (NCT) [NCT3.0_2015.4 TransOnco, NCT3.0_2015.52 DysregPT]
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD. Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro. Strikingly, even PDX with carcinoma histology can host scarce EBV-infected B-lymphocytes that can fully overgrow carcinoma cells during serial passaging in vitro and in vivo. As serial xenografting is crucial to expand primary tumor tissue for biobanks and cohorts for preclinical mouse avatar trials, the emerging dominance of B-lymphoproliferations in serial PDX represents a serious confounding factor in these models. Consequently, repeated phenotypic assessments of serial PDX are mandatory at each expansion step to verify bona fide carcinoma xenografts.
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