A patient-like human malignant pleural mesothelioma nude-mouse model.

Human malignant pleural mesothelioma is an aggressive cancer with no effective treatment. A relevant animal model is required to study the biology and to develop effective treatment. To meet this need we have developed an orthotopic transplant model for malignant mesothelioma in nude mice. Fresh specimens derived from four patients with malignant mesothelioma were implanted on the parietal pleura of nude mice. All xenografted tumors gave rise to locally growing tumors in the mice. The transplanted mice presented with symptoms of malignancy such as decrease in physical activity and signs of tumor-related respiratory distress. These animals were shown to have extensive tumor spread in the ipsilateral and contralateral pleural cavity as well as mediastinal lymph nodes. When the lesions were confined to the ipsilateral parietal pleura, the implanted animals were in good physical condition. The macroscopic features usually found in the patients were also found in the implanted animals such as nodules, masses and pleural thickness. Histologic examination revealed malignant mesothelioma similar to that from which the original tumor specimen was derived. Orthotopic parietal-pleura implantation of fresh histological human malignant mesothelioma thus allows mesothelioma growth in an animal model that mimics the clinical spread of the human disease. This model provides for the first time a useful human model for biological studies of this disease and for developing effective treatment.