Mesothelioma is a rare and aggressive cancer that affects the mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Due to its aggressive nature, mesothelioma has a poor prognosis and limited treatment options. Therefore, preclinical animal models that mimic the human disease are essential for mesothelioma research to develop new therapies, understand disease mechanisms, and test the efficacy of potential treatments.
In vivo models for mesothelioma research can be broadly categorized into two types: xenograft models and genetically engineered mouse models (GEMMs). Xenograft models involve implanting human mesothelioma cells or tissues into immunodeficient mice or rats, while GEMMs are created by genetically modifying mice to develop mesothelioma.
Subcutaneous Xenograft Model: In this model, mesothelioma cells are injected subcutaneously into immunodeficient mice, and tumor growth is monitored. This model is relatively easy to establish, and the tumors can be easily measured and collected for further analysis. However, this model does not fully mimic the human mesothelioma microenvironment and lacks the pleural or peritoneal cavities’ physiological conditions.
Orthotopic Xenograft Model: In this model, mesothelioma cells are injected directly into the pleural or peritoneal cavity of immunodeficient mice. This model more closely mimics the human mesothelioma microenvironment and allows for the study of tumor progression and metastasis. However, the model requires more technical expertise to establish, and tumor growth may be affected by the host’s immune system.
Genetically Engineered Mouse Models (GEMMs):
Conditional Knockout Mouse Model: In this model, a gene or genes involved in mesothelioma development are specifically deleted in mice. This model allows for the study of the specific genes’ role in mesothelioma development and progression. However, the model may not fully mimic the human mesothelioma microenvironment.
Mesothelin-Driven Mouse Model: In this model, mesothelioma is induced in mice by overexpressing mesothelin, a protein found in mesothelioma cells. This model mimics human mesothelioma more closely than other GEMMs and allows for the study of mesothelin’s role in mesothelioma development and progression.
BAP1 Mouse Model: In this model, mice are genetically modified to have a deficiency in the BAP1 tumor suppressor gene, which is commonly mutated in human mesothelioma. This model allows for the study of the role of BAP1 in mesothelioma development and progression.
In conclusion, there are several in vivo models available for mesothelioma research, each with its advantages and disadvantages. Choosing the appropriate model depends on the research goal and the availability of resources and expertise. Nonetheless, these models provide valuable tools to study mesothelioma and develop new therapies for this aggressive cancer.