Am. J. Respir. Cell Mol. Biol., Volume 26, Number 2, February, 2002 189-193

The Presence of Simian-Virus 40 Sequences in Mesothelioma and Mesothelial Cells Is Associated with High Levels of Vascular Endothelial Growth Factor

Paola Cacciotti, Luigi Strizzi, Giovina Vianale, Laura Iaccheri, Roberta Libener, Camillo Porta, Mauro Tognon, Giovanni Gaudino, and Luciano Mutti

Department of Medical Sciences, University of Piemonte Orientale "A. Avogadro," Novara: Department of Oncology and Neurosciences, "G. D'Annunzio" University, Chieti; ASL-¹ 1, Piemonte and IRCSS Maugeri Fondation, Pavia; Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Ferrara; Pathology Service, SS. Antonio e Biagio Hospital, Alessandria; and IRCCS, San Matteo University Hospital, Pavia, Italy

The aim of this study was to evaluate whether the presence of simian virus-40 (SV40) is associated with increased release of vascular endothelial growth factor (VEGF) in human malignant mesothelioma (MM) cells. We studied nine cell lines derived from pleural effusion (PE) of patients with MM, and three different cultures of normal human mesothelial cells (NHMC) derived from pleural fluid of patients with congestive heart failure. NHMC were transfected with full length SV40 (NHMC-FL) or large T antigen (NHMC Tag) DNAs. High levels of VEGF were detected in conditioned media of each of two MM cells that tested positive for SV40 by PCR amplification and Southern blot hybridization and for Tag transcript by reverse transcription- polymerase chain reaction (RT-PCR) and immunoprecipitation. We also found that NHMC-FL released high amounts of VEGF. Conditioned media from SV40-positive MM cells and from FL-NHMC increased proliferation of human umbilical vein cells (HUVEC) and this effect was partially abrogated by adding specific blocking antibodies against VEGF. These results offer the first evidence that SV40 can cause VEGF release in SV40-positive MM cells and that entire viral genome is required for this effect.

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