A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth.
The goal of our study was to raise monoclonal antibodies (mAbs) against endothelial cell-surface proteins specific for tumor vasculature. Here, we describe the generation and intensive characterization of mAb AA98, including its functional properties and its antigen identification. In our study, an enhanced mAb AA98 immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVECs). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared with blood vessels of normal tissues. We identified the AA98 antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146; however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays antiangiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in 3 xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology.
Yan
Xiyun
X
Center of Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China 100101. yanxy@sun5.ibp.ac.cn
Lin
Yun
Y
Yang
Dongling
D
Shen
Yi
Y
Yuan
Mei
M
Zhang
Zhiqiang
Z
Li
Peiyu
P
Xia
Hongtian
H
Li
Li
L
Luo
Dandan
D
Liu
Qin
Q
Mann
Karlheinz
K
Bader
Bernhard L
BL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000494:pharmacology / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000276:immunology; D051929:CD146 Antigen; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019006:Neural Cell Adhesion Molecules; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051929:CD146 Antigen; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules