The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor

Our plain-English summary of The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor, by P. Cacciotti, L. Strizzi, G. Vianale, et al (American Journal of Respiratory Cell and Molecular Biology, 2002).

The study

• Authors: P. Cacciotti, L. Strizzi, G. Vianale, L. Iaccheri, R. Libener, C. Porta, M. Tognon, G. Gaudino, L. Mutti
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2002;26(2):189-93
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This laboratory study by researchers in Italy asked whether the virus SV40 is linked to how much vascular endothelial growth factor (VEGF), a substance that promotes blood-vessel growth, mesothelial cells release. The authors grew cells from the pleural fluid of nine patients with malignant mesothelioma. They also grew normal mesothelial cells from the pleural fluid of three patients with congestive heart failure, and gave these normal cells either the full SV40 genome or only its large T antigen gene. Asbestos exposure was not studied. SV40 DNA was found in two of the nine mesothelioma cell lines. Those two lines, and normal cells carrying the full SV40 genome, released significantly more VEGF (averages of 1579 and 1554 pg/ml) than SV40-negative mesothelioma cells (307 pg/ml) or untreated normal cells (168 pg/ml). Culture medium from SV40-positive mesothelioma cells increased the growth of umbilical vein cells. Adding VEGF-blocking antibodies did not significantly reduce that growth. The authors concluded that SV40 may take part in increased VEGF production. They described this as a possible new way SV40 might favor mesothelioma growth, while stating that the mechanism is unclear.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) cell culture study
• Who was studied: Cell lines from the pleural effusions of nine patients with malignant mesothelioma, and primary normal human mesothelial cell cultures from three patients with transudative pleural fluid due to congestive heart failure and no history of malignant disease; the authors are at Italian institutions
• Exposure: Simian virus 40 (SV40): naturally present in some mesothelioma cell lines, or introduced into normal mesothelial cells as full-length SV40 DNA or as a vector expressing SV40 large T antigen. No asbestos exposure was studied.
• Main results:
  • SV40 early region DNA was found in two of the nine mesothelioma cell lines (MMP and MMCa), which also expressed the T antigen; the T antigen transcript was not detected in the other seven
  • Mean VEGF was significantly higher in SV40-positive mesothelioma cell cultures (1579 pg/ml, SD 367) and in normal cells given full-length SV40 (1554 pg/ml, SD 312) than in SV40-negative mesothelioma cells (307 pg/ml, SD 102), untreated normal cells (168, SD 27), normal cells given an irrelevant plasmid (668, SD 75) and normal cells given T antigen only (815, SD 53)
  • Normal cells given only the T antigen released significantly more VEGF than SV40-negative mesothelioma cells or untreated normal cells; their difference from cells given the irrelevant plasmid was at the limit of statistical significance
  • Normal cells transfected with an irrelevant plasmid also showed increased VEGF
  • Culture medium from SV40-positive mesothelioma cells significantly increased umbilical vein endothelial cell counts at 24 and 48 hours compared with controls
  • Adding VEGF-blocking antibodies to the SV40-positive mesothelioma culture medium did not significantly reduce endothelial cell counts
• The authors' conclusion: The authors concluded that SV40 may participate in increased VEGF production by mesothelial cells and that their findings describe a new mechanism by which SV40 might favor mesothelioma proliferation
• Limitations the authors state:
  • The authors state that how SV40 may be involved in growth-factor regulation is unclear

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesothelial Cells, SV40, Pleural Effusion.

Related studies

• Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma — L. Strizzi, A. Catalano, et al. (2001)
• Presence and expression of the simian virus-40 genome in human giant cell tumors of bone — G. Gamberi, M.S. Benassi, et al. (2000)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)
• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents — V. Levresse, S. Moritz, et al. (1998)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)

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