CD146 is a potential immunotarget for neuroblastoma
Satoshi Obu, Katsutsugu Umeda, Hiroo Ueno, Mari Sonoda, Keiji Tasaka, Hideto Ogata, Kagehiro Kouzuki, Seishiro Nodomi, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Tatsuya Okamoto, Eri Ogawa, Hideaki Okajima, Ken Morita, Yasuhiko Kamikubo, Koji Kawaguchi, Kenichiro Watanabe, Hideto Iwafuchi, Shigeki Yagyu, Tomoko Iehara, Hajime Hosoi, Tatsutoshi Nakahata, Souichi Adachi, Shinji Üemoto, Toshio Heike, Junko Takita
Abstract
Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest-derived immature cells. The prognosis of patients with high-risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti-tumor effects of CD146-targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA-mediated knockdown of CD146, or treatment with an anti-CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor-kappa B signaling pathway. Furthermore, the anti-CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma.