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.
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 humancolon cancer cells.
Authors: H Walczak; M A Degli-Esposti; R S Johnson; P J Smolak; J Y Waugh; N Boiani; M S Timour; M J Gerhart; K A Schooley; C A Smith; R G Goodwin; C T Rauch Journal: EMBO J Date: 1997-09-01 Impact factor: 11.598
Authors: A Oehm; I Behrmann; W Falk; M Pawlita; G Maier; C Klas; M Li-Weber; S Richards; J Dhein; B C Trauth Journal: J Biol Chem Date: 1992-05-25 Impact factor: 5.157
Authors: M A Degli-Esposti; P J Smolak; H Walczak; J Waugh; C P Huang; R F DuBose; R G Goodwin; C A Smith Journal: J Exp Med Date: 1997-10-06 Impact factor: 14.307