Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas
| Autor: | Hidetaka Ohnuki, Karen Aleman, Robert Yarchoan, Vickie Marshall, Thomas S. Uldrick, Mark N. Polizzotto, Denise Whitby, Hyeongil Kwak, Mark Raffeld, Christina M. Annunziata, David Sánchez-Martín, Victoria Wang, Giovanna Tosato, Kathleen M. Wyvill |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Epstein-Barr Virus Infections Herpesvirus 4 Human Cancer Research Epithelial-Mesenchymal Transition viruses Mice SCID Biology Epithelium Mice Young Adult 03 medical and health sciences Mice Inbred NOD immune system diseases Lymphoma Primary Effusion hemic and lymphatic diseases medicine Animals Humans Epstein–Barr virus infection Aged virus diseases Articles Herpesviridae Infections Middle Aged biochemical phenomena metabolism and nutrition medicine.disease Lymphoma Disease Models Animal 030104 developmental biology Oncology Cell culture Herpesvirus 8 Human Monoclonal Cancer research Cytokine secretion Primary effusion lymphoma CD5 Mesothelial Cell |
| Zdroj: | JNCI: Journal of the National Cancer Institute. 109 |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djx016 |
| Popis: | Background Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)-induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear. Methods Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity. Results We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV + or EBV + mesothelial cells. After extended culture (16-17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45 + /B220 + , CD5 + , CD27 + , CD43 + , CD11c + , and CD3 - cells resembling "B1-cells," most commonly found in mouse body cavities. These "B1-like" cells were short lived. However, long-term KSHV + EBV - and EBV + KSHV - clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients' original effusions. Conclusions Mesothelial-to-lymphoid transformation is a newly identified in vitro process that generates "B1-like" cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans. |
| Databáze: | OpenAIRE |
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