GROWTH-FACTOR RESPONSES AND PROTOONCOGENE EXPRESSION OF MURINE MESOTHELIAL CELL-LINES DERIVED FROM ASBESTOS-INDUCED MESOTHELIOMAS

Repeated intraperitoneal injections of crocidolite asbestos fibers ind uced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the developme nt of these tumors. The cell lines isolated from mice with mesotheliom as recapitulated their growth pattern in vivo and were tumorigenic whe n reinjected into syngeneic mice. Similar to human mesothelial cells, growth of the murine cell lines was stimulated by epidermal growth fac tor. Reactive mesothelial cells and mesotheliomas expressed the recept or for this growth factor. Crocidolite asbestos fibers have been repor ted to induce sustained expression of the c-fos and c-jun protooncogen es in rat pleural mesothelial cells in vitro (Heintz et al, Proc. Natl . Acad. Sci. USA 90: 3299-303, 1993). Human malignant mesotheliomas ha ve been shown to express c-fos in situ (Ramael et al, Histol. Histopat hol. 10: 639-643, 1995). Two of the cell lines derived from highly inv asive murine mesotheliomas overexpressed c-fos and c-jun. This murine model recapitulates the histopathology, growth factor responses, and p rotooncogene expression of human malignant mesotheliomas.