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 Kantor, R. R. S. Articles by Ferrone, S. Search for Related Content PubMed PubMed Citation Articles by Kantor, R. R. S. Articles by Ferrone, S.

Biosynthesis and Intracellular Processing of Four Human Melanoma Associated Antigens¹

Department of Human Cancer Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [R. R. S. K., A. P. A.]; Departments of Pathology and Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032 [A. K. N.]; and Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595 [S. F.]

By analyzing human melanoma cells with monoclonal antibodies (MoAb) we have identified four melanoma associated antigens with distinct tissue distribution and structural properties. They include the high molecular weight melanoma associated antigen (MAA), the M_r 120,000 MAA, the M_r 100,000 MAA, and the cytoplasmic MAA defined by MoAb 465.12. Previous studies have shown that these antigens may be useful markers to characterize the biology of melanoma cells and to develop immunodiagnostic and immunotherapeutic approaches to melanoma. In the present investigation pulse-chase intrinsic labeling studies combined with the biosynthetic inhibitor tunicamycin and with enzymatic degradations with endoglycosidase H have shown that the determinants recognized by the MoAb utilized are expressed on the core protein of the molecules. Furthermore the four MAAs are highly glycosylated with N-linked carbohydrate chains and are synthesized as precursors which bear endoglycosidase H-sensitive chains. The high molecular weight (M_r 500,000/280,000) MAA displays a major precursor with a molecular weight of 240,000 which expresses the epitopes recognized by the anti-high molecular weight MAA MoAbs 149.53, 225.28S, and 763.74T. This precursor has an apparent molecular weight of 220,000 when cells are grown in the presence of tunicamycin. The M_r 89,000 and M_r 36,000 subunits of the M_r 125,000 MAA have biosynthetic precursors with molecular weights of 76,000 and 25,000. Endoglycosidase H digestion of the M_r 76,000 precursor produces a M_r 46,000 polypeptide. The M_r 100,000 MAA has a M_r 87,000 biosynthetic precursor. The cytoplasmic MAA (M_r 100,000, 75,000, 72,000, and 25,000) has a single precursor with a molecular weight of 75,000 which appears as a M_r 60,000 polypeptide after endoglycosidase H digestion. Characterization of the biosynthesis of the four MAAs will contribute to the development of approaches to modulate their expression and shedding by melanoma cells.

¹ This work was supported by Grants NIH-CA34031 and CA37959 and by the Oliver S. and Jennie R. Donaldson Charitable Trust.

² Recipient of a National Cancer Institute Postdoctoral Fellowship (1F32CA-06933).

³ To whom requests for reprints should be addressed, at Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595.

Received 2/17/86. Revised 5/30/86. Accepted 7/10/86.

This article has been cited by other articles:

				S. Wagner, C. Hafner, D. Allwardt, J. Jasinska, S. Ferrone, C. C. Zielinski, O. Scheiner, U. Wiedermann, H. Pehamberger, and H. Breiteneder Vaccination with a Human High Molecular Weight Melanoma-Associated Antigen Mimotope Induces a Humoral Response Inhibiting Melanoma Cell Growth In Vitro J. Immunol., January 15, 2005; 174(2): 976 - 982. [Abstract] [Full Text] [PDF]

				M. Geiser, D. Schultz, A. Le Cardinal, H. Voshol, and C. Garcia-Echeverria Identification of the Human Melanoma-associated Chondroitin Sulfate Proteoglycan Antigen Epitope Recognized by the Antitumor Monoclonal Antibody 763.74 from a Peptide Phage Library Cancer Res., February 1, 1999; 59(4): 905 - 910. [Abstract] [Full Text] [PDF]

				E. J. Noronha, X. Wang, S. A. Desai, T. Kageshita, and S. Ferrone Limited Diversity of Human scFv Fragments Isolated by Panning a Synthetic Phage-Display scFv Library with Cultured Human Melanoma Cells J. Immunol., September 15, 1998; 161(6): 2968 - 2976. [Abstract] [Full Text] [PDF]