Researchers from San Raffaele Hospital in Milan, Italy, created and extensively characterized a new mouse model of malignant mesothelioma. The model allows the researchers to study the interactions between cancer cells and the immune system, enabling better studies of the early development of malignant mesothelioma.
The study, “Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells,” was published in the journal Scientific Reports.
Most animal models of malignant mesothelioma are based on the use of human tumor cells transplanted into mice with a compromised immune system. This approach suffers a number of limitations, including the inability to observe interactions between the immune system and tumor cells. As altered immune responses contribute to the development of mesothelioma, it is crucial to study the development of the cancer in animals with an intact immune system.
Instead of using mouse mesothelioma cells derived from tumors that spontaneously developed after mice were exposed to asbestos, the research team used three different mesothelioma cell types and injected them into normal mice.
HMGB1 is a factor released by damaged cells, alerting the immune system to cell death. Cells in the mesothelium release the HMGB1 factor after asbestos exposure, which contributes to the early inflammation known to precede cancer development. Moreover, the tumor needs HMGB1 for ensuing growth.
While targeting HMGB1 could be a way to stop tumor growth, the factor is also part of the immunogenic cell death response – a process whereby anticancer drugs can kill tumor cells by activating the body’s own immune response.
So, the researchers wanted to study how the tumors developed after injection of cancer cells, particularly how they responded to HMGB1. The team also explored the genetic setup and the expression of biomarkers in the tumors.
The team found that the tumors in the mouse model were very similar to their human counterparts. Furthermore, they produced high levels of HMGB1, and responded to the factor in a similar way to human tumors.
The tumors derived from the three cell types expressed in different kinds of markers. Researchers also observed that the tumor cells, while in lab culture, expressed a different set of markers than the established tumor in the mice. The finding mimics earlier observations made in studies on human mesothelioma cells.
Findings also showed that the mesothelioma tumors in the mouse model reacted to treatment in a similar fashion to human malignant mesothelioma.
The authors believe the new mouse model is a valuable tool, and should be used in preclinical research on malignant mesothelioma.