A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells.
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.
Matsukawa
Hidehiko
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, 160-8582, Japan.
Kanai
Takanori
T
Naganuma
Makoto
M
Kamada
Nobuhiko
N
Hisamatsu
Tadakazu
T
Takaishi
Hiromasa
H
Ogata
Haruhiko
H
Mukai
Makio
M
Ishii
Hiromasa
H
Mimori
Tsuneyo
T
Watanabe
Mamoru
M
Hibi
Toshifumi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface