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PLoS One. 2014 Feb 28;9(2):e90349. doi: 10.1371/journal.pone.0090349. eCollection 2014.

Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL).

Author information

1
Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China ; Department of Medicine, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
2
Department of Pathology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
3
Central Laboratory, East Hospital, Tongji University School of Medicine, Shanghai, China.
4
Department of Urology, East Hospital, Tongji University School of Medicine, Shanghai, China.
5
Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China ; Departments of Microbiology, Immunology & Parasitology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.

Abstract

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+) PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

PMID:
24587336
PMCID:
PMC3938717
DOI:
10.1371/journal.pone.0090349
[Indexed for MEDLINE]
Free PMC Article

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