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We have generated two mouse models with profuse lymphomatous effusions that resemble HHV8\u2010unrelated ELBCL occurring in humans, by grafting the cell lines designated as Pell\u20101 and Pell\u20102. Using these in vivo models, we evaluated the potential role of vascular endothelial growth factor (VEGF) in the pathogenesis of HHV8\u2010unrelated ELBCL. Both Pell\u20101 and Pell\u20102 cells consistently produced very high levels of VEGF in mice, in contrast to in vitro findings of relatively low VEGF production in culture medium by HHV8\u2010unrelated ELBCL cells, especially Pell\u20101 cells. Conversely, returning Pell\u20101 cells grown in mice to culture medium markedly suppressed VEGF production to the original in vitro level. These findings suggest that the tumour microenvironment plays a role in the steady production of VEGF. We also found that the interaction between HHV8\u2010unrelated ELBCL cells and peritoneal mesothelial cells increased the production of VEGF in vitro. Finally, we found that bevacizumab significantly suppressed effusion formation and lymphoma cell growth in both mouse models. These results suggest that bevacizumab is a rational approach to the treatment of HHV8\u2010unrelated ELBCL.<\/jats:p>","DOI":"10.1111\/jcmm.17570","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T17:09:30Z","timestamp":1665335370000},"page":"5580-5589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting <scp>VEGF<\/scp> with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8\u2010unrelated effusion large B\u2010cell lymphoma in vivo"],"prefix":"10.1111","volume":"26","author":[{"given":"Fumiya","family":"Ogasawara","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School, Kochi University  Nankoku Japan"},{"name":"Department of Hematology Kochi Medical School, Kochi University  Nankoku 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