Base Mouse Model Established for Mesothelioma
Amsterdam, The Netherlands - Scientists at The Netherlands Cancer Institute in Amsterdam have succeeded in developing a mouse model for human malignant mesothelioma. The team of scientists published results of their research in the March, 2008 issue of Cancer Cell, published by Cell Press.
Mesothelioma is a rare but invariably fatal type of cancer that typically develops in the lining of the lungs. Mesothelioma develops as a direct result of asbestos exposure, but often with a latency period of between twenty and fifty years, and sometimes longer. Mesothelioma cancers are particularly aggressive and resistant to treatment, and the average patient has a very poor prognosis following diagnosis.
When creating a mouse model, scientists attempt to reproduce a human disease in the laboratory, in a strain of test animals. To do this, a team of researchers works with a breed of laboratory mice in which all of the mice are genetically identical. Using genetically identical mice allows scientists to study diseases more effectively, as they can rule out genetic variables that might influence research results.
In humans, mesothelioma is caused by exposure to asbestos, which results in the generation of genetic mutations that eventually give rise to cancer. Malignant mesothelioma has been associated in particular with mutations in genes called neurofibromatosis 2.
In addition, malignant mesothelioma is associated with so-called ‘genetic lesions’ in cellular pathways affected by genes called P53 and RB. Lesions in these genetic pathways prevent cells from regulating cell division properly, which means that cancer is more likely to develop in these cells.
The team of scientists at The Netherlands Cancer Institute tried to mimic malignant mesothelioma in laboratory mice by inducing mutations in the Nf2, p53 and Rb pathways of the mice. They targeted the mesothelial lining of the thoracic cavity, to better mimic the way mesothelioma can develop in humans.
The researchers found that mice with certain types of induced mutations developed malignant mesothelioma tumors following a short latency period. Using a technique called bioluminescence imaging, the scientists found that the cancer the mice developed resembled human malignant mesothelioma very closely. They also discovered that a particular mutation in a gene called Ink4a lead, in mice, to the development of a much more invasive and aggressive type of mesothelioma.
Overall, the results of the study indicate that the research team has succeeded in developing a mouse model for mesothelioma. The model mimics human malignant mesothelioma very closely.
In terms of mesothelioma research, the news is all good. The existence of an accurate mouse model means that teams of mesothelioma researchers have a way of replicating the disease in a non-human patient. This in turn means that research into the way that mesothelioma develops and spreads can be further investigated, and also provides an invaluable tool with which to test new therapies and treatments.
