Simian-Virus 40 Infection Causes Mesothelioma Cells to Secrete VEGF

NEW YORK (Reuters Health) Feb 19 - The integration of simian virus-40 (SV40) DNA sequences into the DNA of human malignant mesothelioma cells is associated with increased release of vascular endothelial growth factor (VEGF), Italian investigators have discovered.

This previously rare tumor is increasing dramatically worldwide, Dr. Luciano Mutti, of the Ospedale S. Pietro e Paolo in Borgosesia, and associates note in the American Journal of Respiratory Cell and Molecular Biology for February. It has been suggested that the link between the cancer and SV40 is associated with contaminated stocks of polio vaccine.

Dr. Mutti's team found that two of nine human malignant mesothelioma cell lines carried SV40 DNA. Mean VEGF levels in the culture medium were significantly higher in the SV40-positive tumor cell cultures than in those that were SV40-negative, 1579 pg/mL versus 307 pg/mL (p < 0.01).

The investigators transfected normal human mesothelial cells with SV40. Their production of VEGF was essentially the same as that of the malignant cells, 1554 pg/mL.

To evaluate the potential angiogenic effect of SV40-positive mesothelioma tumors, the authors incubated human umbilical vein cells with the medium in which cells positive and negative for SV40 had been cultured. The SV40-positive culture medium induced significantly greater cell growth at 24 and 48 hours than did the SV40-negative medium (p < 0.01).

Using antibodies to block VEGF did not reduce the cell counts, however, suggesting that "VEGF may not be the only growth factor produced by malignant mesothelioma cells capable of stimulating endothelial cell growth," the Italian team adds. Therefore, the group recommends research be conducted to look for anti-angiogenic agents for the treatment of this tumor.

Drs. Brooke T. Mossman and Dieter C. Gruenert, of the University of Vermont College of Medicine in Burlington, suggest, "The establishment of a favorable tumor environment may be relevant to both asbestos- and SV40-induced mesotheliomas and may be one mechanism whereby SV40 acts cooperatively with asbestos in the development of these malignancies."

Am J Respir Cell Mol Biol 2002;26:167-169,189-193.

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