Abstract
Malignant mesothelioma (MM) is a tumor mostly caused by asbestos exposure. There are several theories of carcinogenesis, including oxidative stress theory. Macrophages phagocytize inhaled asbestos as a foreign material, but cannot digest them and generate reactive oxygen species with frustration. We previously reported that long-lasting oxidative stress via local excess iron damages mesothelial cells and cause MM carcinogenesis. MM is one of the most aggressive tumors. We recently reported that the levels of connective tissue growth factor (CTGF) correlates with its malignancy in asbestos-induced MM in rats. CTGF is a secretory protein and overexpressed in several desmoplastic tumors. Hippo, TGF-β and Wnt pathways are known to be involved in CTGF transcriptional regulation. In Wnt pathway, CTGF binds to LRP6 on plasma membrane and activates an autocrine loop, thereby enhancing tumor malignancy. Human CTGF-specific monoclonal antibody (FG-3019, FibroGen, Inc.) attenuates malignant properties of several tumors and is in clinical trial for the treatment of pancreatic cancer. In this study, we studied the effect of FG-3019 on MM in vitro and in vivo. In in vitro study, anticancer effect of FG-3019 was marginal. However, we obtained statistically significant results in in vivo study. Further studies are in progress in our laboratory.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call