Cell surface glycoprotein associated with human lung tumors that is similar to but distinct from the epidermal growth factor receptor.
A cell surface glycoprotein (gp160) present on the surface of non-small cell human lung tumors is characterized and compared with the epidermal growth factor receptor (EGFR). The epitope on gp160 recognized by monoclonal antibody 5E8 is shown to be part of the protein moiety of the molecule and is found to be relatively stable. The epitope is stable over a wide pH range and after treatment with urea as well as most ionic and non-ionic detergents. We have observed that gp160 is similar in several respects to the EGFR. However, despite the similarities, several independent lines of experimental evidence presented here suggest that gp160 and the EGFR are distinct molecules. The first evidence suggesting that these two molecules are different is that the EGFR, but not gp160, is constitutively detectable in the A431 cell tissue culture supernatant, and that a pulse of these cells with epidermal growth factor (under conditions which permit the internalization of the receptor-ligand complexes) significantly reduces the expression of the EGFR without noticeably affecting the level of gp160 on the cell surface. Two very different immunofluorescent patterns marking the position of gp160 and EGFR are observed using monoclonal antibodies specific for each molecule. Using an enzyme-linked immunosorbent assay, it was determined that these same monoclonal antibodies do not cross-inhibit one another, and it was established that gp160, but not EGFR, was retained on an affinity column containing anti-gp160 antibodies immobilized to the solid matrix. An additional finding that supports the notion that gp160 and the EGFR are distinct molecules is that one human lung tumor cell line (Calu-3) has been identified which expresses gp160 but not the EGFR on its surface. These results indicate that there are characteristics which distinguish gp160 from the EFGR, and we establish here that these distinguishing features reflect differences at the protein moiety and not simply differential glycosylation. We conclude from these studies that we have identified and characterized a cell surface molecule that resembles in several respects the epidermal growth factor receptor. This cell surface molecule represents a potentially useful target for the immunotherapy and diagnosis of human non-small cell lung cancer.
Chen
F A
FA
Department of Molecular Immunology and Thoracic Surgery, Roswell Park Memorial Institute, Buffalo, New York 14263.
Repasky
E A
EA
Takita
H
H
Schepart
B S
BS
Bankert
R B
RB
D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology; D006801:Humans; D007158:Immunologic Techniques; D008175:Lung Neoplasms / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D012995:Solubility
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D066246:ErbB Receptors