Cloning and Expression of the Tumor-Associated Antigen L6

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 8; pp. 3503 - 3507
• Main Authors: Marken, John S., Schieven, Gary L., Hellstrom, Ingegerd, Hellstrom, Karl Erik, Aruffo, Alejandro
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.04.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Animals; Antigens; Antigens, Neoplasm - genetics; Antigens, Surface - analysis; Antigens, Surface - genetics; Base Sequence; Biological and medical sciences; Cancer; carcinoma; Cell Line; Cell lines; Cloning, Molecular; Colonic Neoplasms; Complementary DNA; COS cells; Deoxyribonucleic acid; DNA; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Flow Cytometry; Fluorescent Antibody Technique; Gene Library; genes; Host-tumor relations. Immunology. Biological markers; Human umbilical vein endothelial cells; Humans; Immunity (Disease); Medical research; Medical sciences; Membrane proteins; Molecular Sequence Data; Molecular Weight; Myeloid cells; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Protein Conformation; RNA, Messenger - genetics; RNA, Messenger - isolation & purification; Sequence Homology, Nucleic Acid; Surface antigens; T lymphocytes; Transfection; Tumors; Vertebrata; Mammalia; Carcinoma; Tumor associated antigen; Complementary DNA; Mouse; Rodentia; Primary structure; Tumor; Colon; Molecular cloning; Cell surface
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.8.3503

The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts. Its molecular nature has, however, remained elusive. Here we describe the expression cloning of a cDNA encoding the L6 antigen. COS cells transfected with this cDNA direct the expression of an ≈24-kDa surface protein that reacts with the two anti-L6 monoclonal antibodies available. The predicted L6 peptide sequence is 202 amino acids long and contains three predicted NH2-terminal hydrophobic transmembrane regions, which are followed by a hydrophilic region containing two potential N-linked glycosylation sites and a COOH-terminal hydrophobic transmembrane region. The L6 antigen is related to a number of cell surface proteins with similar predicted membrane topology that have been implicated in cell growth. Two other members of this family of proteins, CD63 (ME491) and CD-029, are also highly expressed on tumor cells. The present findings should make it possible to further study the role of the L6-defined antigen in normal and neoplastic cells and to construct animal models for development of improved agents for active and passive cancer immunotherapy.