16 Jul Aspirin Inhibits Growth of Mesothelioma Cells in Mouse Model
Medical Research: What is the background for this study?
Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers. When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space. HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy. Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth. In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth. Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013). We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth.
Medical Research: What are the main findings?
Dr. Yang: We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition. We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.
Medical Research: What should clinicians and patients take away from your report?
Dr. Yang: Recent studies conclusively demonstrated that taking daily aspirin reduces the incidence of colon cancer and of other inflammatory related malignancies -which are often associated with increased HMGB1 levels. Our results provide a mechanistic rationale to these findings indicating that the anticancer activity of aspirin is at least in part related to its ability to inhibit HMGB1. Preliminary and unpublished results in our laboratory suggest that aspirin does not significantly influence the aggressive growth of large late stage mesothelioma tumors in mice. Instead, we suggest that aspirin may be effective to decrease tumor growth in the early stages of mesothelioma development. Moreover, similarly to patients at high risk for colon cancer, patients at high risk for mesothelioma, for example, workers who have been exposed to asbestos, may benefit from daily aspirin taken over the course of several years.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Yang: We are planning a clinical trial to see if aspirin can reduce the serum levels of HMGB1 in asbestos exposed individuals. If the trial will be successful, it will be important to perform a larger trial to see if aspirin reduces the incidence of mesothelioma. We should focus on a cohort of individuals exposed to asbestos, because of their high risk of developing mesothelioma, and we would like to conduct this clinical trial to test the hypothesis that daily aspirin may reduce or delay the incidence of mesothelioma.
Yang H1, Pellegrini L1, Napolitano A2, Giorgi C3, Jube S1, Preti A4, Jennings CJ1, De Marchis F4, Flores EG1, Larson D1, Pagano I1, Tanji M1, Powers A1, Kanodia S5, Gaudino G1, Pastorino S1, Pass HI6, Pinton P3, Bianchi ME4, Carbone M1.
Haining Yang MD Ph.D (2015). Aspirin Inhibits Growth of Mesothelioma Cells in Mouse Model