A PATIENT-LIKE HUMAN-MALIGNANT PLEURAL MESOTHELIOMA NUDE-MOUSE MODEL

Human malignant pleural mesothelioma is an aggressive cancer with no e ffective treatment. A relevant animal model is required to study the b iology and to develop effective treatment. To meet this need we have d eveloped an orthotopic transplant model for malignant mesothelioma in nude mice. Fresh specimens derived from four patients with malignant m esothelioma were implanted on the parietal pleura of nude mice. All xe nografted tumors gave rise to locally growing tumors in the mice. The transplanted mice presented with symptoms of malignancy such as decrea se in physical activity and signs of tumor-related respiratory distres s. These animals were shown to have extensive tumor spread in the ipsi lateral and contralateral pleural cavity as well as mediastinal lymph nodes. When the lesions were confined to the ipsilateral parietal pleu ra, the implanted animals were in good physical condition. The macrosc opic features usually found in the patients were also found in the imp lanted animals such as nodules, masses and pleural thickness. Histolog ic examination revealed malignant mesothelioma similar to that from wh ich the original tumor specimen was derived. Orthotopic parietal-pleur a implantation of fresh histological human malignant mesothelioma thus allows mesothelioma growth in an animal model that mimics the clinica l spread of the human disease. This model provides for the first time a useful human model for biological studies of this disease and for de veloping effective treatment.