Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras

Tang, Yunlian; He, Rongfang; Zhang, Yang; Liu, Fang; Cheng, Ailan; Wu, Yimou; Gan, Runliang

doi:10.1186/1743-422x-8-213

Cited by 9 publications

(8 citation statements)

References 18 publications

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“…HMs can also be generated by the direct injection of human peripheral blood. In one early cancer study, Tang, et al injected purified human blood lymphocytes from donors infected with Epstein-Barr virus into SCID mice and monitored these animals for indications of human B cell lymphoma (20). In other cases, mice are classified as humanized after the implantation of human stromal tissue together with the tumor tissue.…”

Section: State Of the Art In Cancer Researchmentioning

confidence: 99%

Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap

et al. 2016

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Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in the context of a human immune system and resultant tumor microenvironment, and recent studies have highlighted the increased similarities in attendant tumor structure, metastasis, and signaling to those features in cancer patients. This setting also facilitates the examination of investigational cancer therapies, including new immunotherapies. This review discusses recent advancements in the generation and application of HM models, their promise in cancer research, and their potential in generating clinically relevant treatments. This review also focuses on current efforts to improve HM models by engineering mouse strains expressing human cytokines or HLA proteins, and implanting human bone, liver, and thymus tissue to facilitate immune cell maturation and trafficking. Finally, we discuss how these improvements may help direct future HM model cancer studies.

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Section: State Of the Art In Cancer Researchmentioning

confidence: 99%

Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap

et al. 2016

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“…This indicated that the induced tumors originated from human cells rather than mouse cells. In our previous study, the concentration of human IgG in the sera of hu‐PBL/SCID chimeric mice was monitored continuously, and the results showed that the levels of IgG gradually increased with the growth of the induced tumors [Tang et al, ].…”

Section: Discussionmentioning

confidence: 99%

Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein–Barr virus‐associated lymphomas

Zhang

Peng

Tang

et al. 2016

Journal of Medical Virology

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Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO-negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. © 2016 Wiley Periodicals, Inc.

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“…In vitro experiments have demonstrated that EBV can transform and even immortalize normal human peripheral lymphocytes [10]. Our group was among the first to transplant EBV-infected human peripheral lymphocytes (hu-PBL) from healthy blood donors into severe combined immunodeficiency (SCID) mice to induce the generation of human-derived B cell lymphomas [11,12]. However, the cellular and molecular mechanisms of malignant transformation of normal lymphocytes and tumor formation induced by EB virus remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Screening and functional analysis of differentially expressed genes in an animal model ofEBV-associated lymphomas

Zhang

Wang

Liu

et al. 2019

Preprint

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Abbreviations: EBV--Epstein-Barr virus; PBL--peripheral blood lymphocyte; SCID--severe combined immunodeficiency mouse, LMP--latent membrane protein, EBER--EBV-encoded small RNAs Abstract Epstein-Barr virus (EBV) is an important human oncogenic virus. This paper is to explore how EBV induce malignant transformation of human lymphocytes and the related mechanism of lymphomagenesis. We have constructed hu-PBL/SCID chimeric mice and established a model of EBV-associated humanderived lymphomas. By using Agilent human whole genome microarray and a series of bioinformatic analyses, a total of 202 differentially expressed genes were screened from the EBV-induced lymphomas in hu-PBL/SCID mice, including 44 up-regulated and 158 down-regulated genes. Calculation of the rank score (RS) values of these genes in the HIPPIE protein interaction networks showed that topoisomerase II alpha (TOP2A), ubiquitin like with PHD and ring finger domains 1 (UHRF1), histone cluster 2 H2B family member E (HIST2H2BE), phosphoglycerate dehydrogenase (PHGDH), vinculin (VCL), insulin-like growth factor 1 receptor (IGF1R), Fos proto-oncogene (FOS), snail family transcriptional repressor 1 (SNAI1), PDZ binding kinase (PBK), and ring finger protein 144B (RNF144B) were the top 10 key node genes of EBV-induced lymphoma. In which, PBK, an up-regulated genes with the highest number of GO annotations, was verified by cellular function experiments and clinical lymphoma samples. Author summaryEB virus is closely associated with human lymphoma and nasopharyngeal carcinoma.Since the susceptible hosts of EBV limit to human and cottontop tammarins, there are no appropriate animal models so far to study the EBV-associated oncogenesis. In our previous experiments, the EBV-associated lymphomas were induced in hu-PBL/SCID chimera (a new humanized mouse model). However, the cellular and molecular mechanisms of malignant transformation of normal human cells and tumor formation induced by EBV remain unclear. In this study, we examined and compared the gene expression profiles of EBV-induced lymphomas and normal human lymphocytes of the same origin in SCID mice. By constructing the gene-function relationship network, we preliminarily found that TOP2A, UHRF1, HIST2H2BE, PHGDH, VCL, IGF1R, FOS, SNAI1, PBK, and RNF144B may be the key genes in EBV-induced lymphomas. These findings suggest that the induction of lymphoma by EBV is a complex process that involves multiple genes and pathways.

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Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras

Cited by 9 publications

References 18 publications

Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap

Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap

Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein–Barr virus‐associated lymphomas

Screening and functional analysis of differentially expressed genes in an animal model ofEBV-associated lymphomas

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