Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver

Abstract

3-Nitrotyrosine (3-NT), a product of peroxynitrite reaction, is abundantly observed in hepatocytes adjacent to human metastatic colorectal carcinoma. To elucidate its biological significance, we undertook to identify nitric oxide (NO)-producing cells and apoptosis under oxidative stress. We observed strong inducible NO-synthase (iNOS) immunoreactivity in the hepatocytes adjacent to metastatic tumor, revealing an identical pattern to 3-NT immunostaining. Furthermore, intense 3-NT immunostaining of hepatocytes was associated with apoptosis whereas carcinoma cells near those hepatocytes presented high proliferating-cell nuclear antigen. Our results suggest that contact of metastatic tumor induces apoptosis in adjacent hepatocytes through peroxynitrite, thus permitting the proliferation of cancer cells.