novel therapeutic strategy with anti-CD9 antibody in gastric cancers

• Published in: Journal of gastroenterology Vol. 44; no. 9; pp. 889 - 896
• Main Authors: Nakamoto, Taisei, Murayama, Yoko, Oritani, Kenji, Boucheix, Claude, Rubinstein, Eric, Nishida, Makoto, Katsube, Fumie, Watabe, Kenji, Kiso, Shinichi, Tsutsui, Shusaku, Tamura, Shinji, Shinomura, Yasuhisa, Hayashi, Norio
• Format: Journal Article
• Language: English
• Published: Japan Japan : Springer Japan 01.09.2009; Springer Japan; Springer Nature B.V
• Subjects: Abdominal Surgery; Angiogenesis Inhibitors - immunology; Angiogenesis Inhibitors - pharmacology; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, CD - immunology; Antigens, CD34 - immunology; Apoptosis - drug effects; Cell Proliferation - drug effects; Colorectal Surgery; Female; Gastroenterology; Hepatology; Humans; Immunoglobulin G - immunology; Immunoglobulin G - pharmacology; In Situ Nick-End Labeling; Medicine; Medicine & Public Health; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Original Article—Alimentary Tract; Stomach Neoplasms - drug therapy; Stomach Neoplasms - immunology; Surgical Oncology; Tetraspanin-29; Xenograft Model Antitumor Assays; CD9; Tumorigenicity; Proliferation; Tetraspanin
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-009-0081-3

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 10⁶ 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 μg/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 mm³ versus 4,507 ± 1,012 mm³; 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/mm² versus 1,135,043 ± 36,086 pixels/mm²; 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.