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Int J Cancer. 2017 Mar 15;140(6):1356-1363. doi: 10.1002/ijc.30561.

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation.

Author information

1
Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
German Cancer Consortium (DKTK), Heidelberg, Germany.
3
Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
4
Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
5
Department of Applied Bioinformatics, NCT Heidelberg and DKFZ, Heidelberg, Germany.
6
Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Heidelberg, Germany.
7
Institute of Pathology, Technische Universität München (TUM), Munich, Germany.
8
DKTK, Munich, Germany.
9
Department of Medical Oncology, NCT Heidelberg, Heidelberg, Germany.
10
Department of Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany.

Abstract

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-Prkdcscid Il2rgtm1Wjl /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.

KEYWORDS:

colorectal cancer; lymphoproliferation; pancreatic cancer; patient-derived xenograft

PMID:
27935045
DOI:
10.1002/ijc.30561
[Indexed for MEDLINE]
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