title: Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sanchez-Martin
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Hyeongil
authors.initials: H
authors.lastname: Kwak
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ohnuki
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.affiliation: Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Annunziata
authors.affiliation: Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wang
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Vickie A
authors.initials: VA
authors.lastname: Marshall
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000473:pathology*; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology; D006566:Herpesviridae Infections / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D055815:Young Adult