Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver.
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.
Kondo
Shohei
S
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Toyokuni
Shinya
S
Tsuruyama
Tatsuaki
T
Ozeki
Munetaka
M
Tachibana
Tsuyoshi
T
Echizenya
Michiko
M
Hiai
Hiroshi
H
Onodera
Hisashi
H
Imamura
Masayuki
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D017209:Apoptosis; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009566:Nitrates; D016877:Oxidants; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II