A novel therapeutic strategy with anti-CD9 antibody in gastric cancers.
BACKGROUND
CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as motility, cell signaling, proliferation, adhesion, and metastasis. However, very little is known about the involvement of CD9 in the process of development of primary tumors. In the present study, we investigated whether anti-CD9 monoclonal antibody (ALB6) has antitumor effects in human gastric cancer cell xenografts.


METHODS
Human gastric cancer cell lines (MKN-28) (5 x 10(6) cells/animal) were inoculated subcutaneously into the dorsal region of SCID mice (five mice in each group). After a tumor was visualized, animals were assigned to either the ALB6 treatment group or the control IgG treatment group (100 microg/body/time, intravenous, three times per week. Day 1, 4, and 7 of first week). Then tumor volumes were monitored every day. Proliferation of tumor was analyzed by 5-bromo-2'-deoxyuridine (BrdU) immunostaining, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) methods, and angiogenesis was assessed by counting the number of CD34-positive endothelial cells.


RESULTS
Tumor volume was significantly suppressed (1,682 +/- 683 mm(3) versus 4,507 +/- 1,012 mm(3); P = 0.049), the BrdU labeling indexes were significantly decreased (10.9 +/- 1.1% versus 17.2 +/- 1.4%; P = 0.009), the apoptotic indexes were significantly increased (1.98 +/- 0.48% versus 0.72 +/- 0.09%; P = 0.034), and tumor microvessel densities were significantly suppressed (671,922 +/- 34,505 pixels/mm(2) versus 1,135,043 +/- 36,086 pixels/mm(2); P = 0.037) in the ALB6 treatment group compared with the control IgG treatment group.


CONCLUSIONS
These results suggest that administration of anti-CD9 antibody to mice bearing human gastric cancer cells successfully inhibits tumor progression via antiproliferative, proapoptotic, and antiangiogenetic effects.
Nakamoto
Taisei
T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan.
Murayama
Yoko
Y
Oritani
Kenji
K
Boucheix
Claude
C
Rubinstein
Eric
E
Nishida
Makoto
M
Katsube
Fumie
F
Watabe
Kenji
K
Kiso
Shinichi
S
Tsutsui
Shusaku
S
Tamura
Shinji
S
Shinomura
Yasuhisa
Y
Hayashi
Norio
N
D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology; D060245:Tetraspanin 29; D023041:Xenograft Model Antitumor Assays
C546418:ALB6 monoclonal antibody; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29