CONTEXT: RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts. OBJECTIVE: To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues. DESIGN: Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression. RESULTS: More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non-tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation. CONCLUSIONS: High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.
CONTEXT: RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts. OBJECTIVE: To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues. DESIGN: Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression. RESULTS: More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non-tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation. CONCLUSIONS: High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.
Authors: Mohamed G Shoreibah; Crystal L Jackson; Paul W Price; Richard Meagher; Andrew K Godwin; Qi Cai; Jeffrey C Gildersleeve Journal: Stem Cells Dev Date: 2010-11-08 Impact factor: 3.272