In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated.The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor.These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma tumor initiating cells.Malignant mesothelioma is an aggressive neoplasm arising from the surface serosal cells of the pleural, peritoneal, and pericardial cavities. Asbestos exposure has been established as the primary cause of mesothelioma; however, there is a long latency period of 30-45 years between exposure to asbestos and development of disease. Workers in the shipyard industry, insulation workers, construction workers, and asbestos miners and manufacturers seem to be at highest risk for developing the disease. Many investigators have suggested that Simian virus 40 (SV40), originating from contaminated poliovirus vaccines that were administered in USA and some European countries between 50's and 70's, might function as a cocarcinogen involved in the development of the disease. However, the relationship between SV40 and mesothelioma remai