De-glycosylation of mucins may expose new tumorassociated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MA
A new cancer-associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain
✍ Scribed by Yoshito Yamashita; Yong Suk Chung; Tetsuji Sawada; Yasuyuki Kondo; Koji Hirayama; Akimasa Inui; Bunzo Nakata; Masahiro Okuno; Ryuichi Horie; Takashi Saito; Keiichi Murayama; Reiji Kannagi; Michio Sowa
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 985 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (Flα‐75) against an artificially designed antigen (Flα), using organic‐synthetic chemistry methods and hybridoma technology. Flα (GalβI → 4GlcNAcβI → 6GalNAαI → Ser/Thr) belongs to core type 6 of O‐linked glycans, which has not been previously reported in human cancers. To produce antibodies against Flα, a glycolipid was synthesized which carries the carbohydrate portion of Flα on a ceramide foundation (GalβI → 4GlcNAcβI → 6GalNAcαI → Cer). The MAbs we obtained (Flα‐75, Flα‐87) specifically recognized Flα and had only a very weak or no cross‐reactivity with other glycolipids similar to Flα. We investigated the expression of Fin in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. Flα was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with Flα‐75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. Flα‐75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, Flα‐75 reacted with the pyloric glands of the stomach, the centro‐acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.
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