Simian virus 40 and human tumors: It is time to study mechanisms

Several studies found simian virus 40 (SV40) in 47% to 83% of human mesothe liomas. Mesotheliomas are malignant tumors of the pleura and peritoneum, fi rmly associated with asbestos exposure. In this issue, Gazdar and colleague s [Shivapurkar et al., 1999] found that SV40 is present only in the maligna nt cells and not in the surrounding stromal cells. Using the microdissectio n technique, they found SV40 in 54% of 93 mesotheliomas of the epithelial t ype. The surrounding reactive stromal cells, (20 lung cancers and 14 mesoth eliomas of the sarcomatoid/fibrous type) did not contain SV40, confirming t he specificity of their positive findings. Furthermore, SV40 was found in 1 4% of 14 non-malignant reactive mesothelial cell proliferations. In 12 case s of mesothelioma a noninvasive (or in situ) component was also identified. In all four cases in which SV40 sequences were present in the invasive com ponent, sequences were also present in the accompanying noninvasive compone nt. These data suggest that the virus resides in the mesothelial cells prio r to tumor development. The data address the remaining concerns raised at a n International Meeting organized by the NIH, FDA, and CDC in 1997 to defin itively associate SV40 with human mesothelioma. It is time now to investiga te the pathogenic mechanisms of th is association, and if SV40-infected mes othelial cells are more susceptible to other carcinogens, such as asbestos. Furthermore, we must investigate the interaction between the host immune s ystem and SV40-infected mesothelial cells, and study if the immunosuppressi ve activity of asbestos interferes with tumor rejection. These studies shou ld lead to a better understanding of mesothelioma pathogenesis, and possibl y to new therapeutic approaches aimed at interfering with the expression of the SV40 genome and/or at eliciting a strong immune response against SV40 infected mesothelial cells.(C) 1999 Wiley-Liss, Inc.