Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model

Malignant pleural mesothelioma is an aggressive tumor that is essentially unresponsive to standard medical and surgical therapies. Little is actually known about its biologic response to therapeutic interventions, in part because of a lack of a "patient-like" animal tumor model. Most experimental models thus far have been derived from inhalation or inoculation of asbestos fibers into animal subjects or by subcutaneous transplantation of human mesothelial cell lines into nude mice. These models are not representative of clinical malignant pleural mesothelioma. In this report, an animal model of human pleural malignant mesothelioma obtained by orthotopic transplantation of intact pleural tumor tissue into athymic nude mice is described. Pleural tumor obtained by thoracoscopy from a patient with epithelial-type malignant pleural mesothelioma was implanted as intact tissue by surgical orthotopic implantation (SOI) into the right pleural cavity of nude mice. Animals were sacrificed when moribund or 6 months after implantation. Tumor growth and regional spread in the mice evaluated at postmortem examination mimicked the clinical pattern of progression of human disease. Histologic findings and the immunohistochemical profile were similar to those demonstrated on examination of thoracoscopic parietal pleural biopsy specimens and post-mortem examination of the original patient's tumor. This "patient-like" nude mouse model of epithelial-type malignant pleural mesothelioma, phenotypically similar to the original human tumor, should facilitate future investigation of tumorigenesis and metastatic potential of this neoplasm. The model should serve as a basis for assessing the impact of experimental and existing therapy on malignant mesothelioma.