title: Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma: relevance to chemo-immunotherapy.
abstract: Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an anti-tumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl LewisA (sLeA) and sialyl LewisX (sLeA) antigens, the complement restriction factors (CD59, CD46 and CD55) and the apoptosis associated factors Fas and Fas Ligand. Sialyl Lewis antigens (sLeA and sLeX), are immunogenic in that they elicit complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and FasL on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLeX was higher than that of sLeA and SCC71 had a very low level of sLeA expression. Both cell lines expressed a high density of CD59 and slightly lower levels of CD46 and CD55 on the cell surface, suggesting that even if host antibodies are accessible to the target antigens such as sLeX, they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles 90033, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Ravindranath
authors.forename: K
authors.initials: K
authors.lastname: Nishimoto
authors.forename: K
authors.initials: K
authors.lastname: Chu
authors.forename: C
authors.initials: C
authors.lastname: Shuler
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D018395:CA-19-9 Antigen; D018958:CD55 Antigens / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005647:Fucosyltransferases / Q000378:metabolism; D005732:Gangliosides / Q000032:analysis*; D006801:Humans; D007167:Immunotherapy; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis*; D009062:Mouth Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013535:Suspensions; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000032:analysis
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D018395:CA-19-9 Antigen; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005732:Gangliosides; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D000080506:Sialyl Lewis X Antigen; D013535:Suspensions; D019014:fas Receptor; C094688:sialyl Lewis(x) ganglioside; C064564:sialyl Le(a) ganglioside; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase