This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sakurai, Y. Articles by Abe, O. Search for Related Content PubMed PubMed Citation Articles by Sakurai, Y. Articles by Abe, O.

Selection of a Monoclonal Antibody Reactive with a High-Molecular-Weight Glycoprotein Circulating in the Body Fluid of Gastrointestinal Cancer Patients¹

Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104 [Yo. S., S. H., Yu. S.], and Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 [S. K., O. A.], Japan

The monoclonal antibody NCC-CO-450 (IgM ) was selected by screening of reactivity with high-molecular-weight antigens (M_r > 10⁶) isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Le^a, Le^x, Le^Y, Tn, sialyl-Le^a, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.

¹ This investigation was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for the Comprehensive Ten-Year Strategy for Cancer Control, Japan, and by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.

² Awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

³ To whom requests for reprints should be addressed.

Received 12/31/87. Revised 4/ 7/88. Accepted 4/13/88.

This article has been cited by other articles:

				S. Koyano, Y. Saito, M. Nagano, K. Maekawa, Y. Kikuchi, N. Murayama, T. Fujino, S. Ozawa, T. Nakajima, K. Matsumoto, et al. Functional Analysis of Three Genetic Polymorphisms in the Glucocorticoid Receptor Gene J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 110 - 116. [Abstract] [Full Text] [PDF]