A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells |
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| Authors: | Hidehiko Matsukawa Takanori Kanai Makoto Naganuma Nobuhiko Kamada Tadakazu Hisamatsu Hiromasa Takaishi Haruhiko Ogata Makio Mukai Hiromasa Ishii Tsuneyo Mimori Mamoru Watanabe Toshifumi Hibi |
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| Institution: | (1) Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan;(2) Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;(3) Department of Pathology, School of Medicine, Keio University, Tokyo, Japan;(4) Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan |
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| Abstract: | Background Apoptosis is a crucial element in the behavior of mammalian cells in many different situations. We here report the establishment
of a novel monoclonal antibody (anti-LHK mAb) that has apoptosis-inducing activity against colon cancer Colo205 cells.
Methods The mechanism of anti-LHK mAb-induced cell death was assessed by microscopic morphology, Annexin V/Hoechst 33528 staining,
and detection of DNA fragmentation. The molecular weight of LHK antigen was determined by Western blotting. Growth inhibition
of Colo205 cells induced by anti-LHK mAb was determined by in vitro and in vivo studies.
Results Anti-LHK reacted with a 70-kDa antigen and completely blocked the proliferation of Colo205 cells bearing LHK in vitro in a
manner characteristic of apoptosis. Strikingly, anti-LHK mAb suppressed tumor growth in a murine peritoneal dissemination
model.
Conclusions LHK antigen, which is restricted to epithelial cells, may be a novel death receptor that plays a critical role in controlling
the growth, invasion, and metastasis of human colon cancer cells. |
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| Keywords: | anti-LHK mAb apoptosis Fas colon cancer |
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