MABT65 Sigma-AldrichAnti-CEACAM1 Antibody, clone 4D1/C2

Recent studies have challenged the previously postulated concept of a tumor-suppressive effect of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). A possible angiogenic influence of CEACAM-1 in non-small-cell lung cancer (NSCLC) has not been investigated so far. Therefore, we examined microvessel density (MVD) and CEACAM-1 expression in primary NSCLC and analyzed their possible correlations under consideration of their prognostic effects. Specimens from 82 consecutive patients with completely resected NSCLC were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2 and the monoclonal anti-CD31 antibody JC70A. The prognostic relevance of CEACAM-1 expression and MVD was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 75 months (range 10-156 months). A high MVD (i.e., > or =31microvessels/400x microscopic field) was observed more frequently in tumors with high CEACAM-1 expression (i.e., >/=66% stained tumor cells) than in tumors with low CEACAM-1 expression (61.8% vs. 33.3%, respectively; p=0.01). In univariate survival analyses, high CEACAM-1 expression and high MVD were associated with development of distant metastasis (p=0.011 and 0.022, respectively) and decreased cancer-related survival (p=0.046 and 0.006, respectively). Multivariate Cox regression analysis demonstrated that the prognostic impact of CEACAM-1 depended on the prognostic influence of MVD, while MVD itself represented an independent prognosticator for unfavorable cancer-related survival (p=0.021; relative risk 2.1; 95% confidence interval, 1.1-4.0). Here we show for the first time that high CEACAM-1 expression is associated with an increased angiogenic activity in NSCLC, and that the prognostic influence of CEACAM-1 might be derived from this association.

The CEA-related cell adhesion molecule 1, CEACAM1, is a glycoprotein expressed on the surface of human granulocytes and lymphocytes, endothelia, and many epithelia. CEACAM1 is involved in the regulation of important biological processes, such as tumor growth, angiogenesis, and modulation of the immune response. CEACAM1, a member of the immunoglobulin superfamily carries several Lewis x (Lex) structures as we recently demonstrated by mass spectrometry of native CEACAM1 from human granulocytes. Since Lex residues of pathogens bind to the C-type lectin dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) expressed on human DCs, we hypothesized that Lex glycans of CEACAM1 are recognized by DC-SIGN. Here, we demonstrate that CEACAM1, the major carrier of Lex residues in human granulocytes, is specifically recognized by DC-SIGN via Lex residues mediating the internalization of CEACAM1 into immature DCs. Expression studies with CEACAM1 in combination with different fucosyltransferases (FUTs) revealed that FUTIX plays a key role in the synthesis of Lex groups of CEACAM1. As Lex groups on CEACAM1 are selectively attached and specifically interact with DC-SIGN, our findings suggest that CEACAM1 participates in immune regulation in physiological conditions and in pathological conditions, such as inflammation, autoimmune disease, and cancer.

mAb directed against the CD66 cluster of granulocyte differentiation Ag recognize Ag of the carcinoembryonic Ag family. A major Ag in extracts from granulocyte membranes bound by CD66 antibodies exhibits a relative molecular mass of 160,000. According to recent data, this Ag may be a product of the biliary glycoprotein (BGP) gene that belongs to the CEA gene family. As a result of alternative splicing, the BGP gene is transcribed into at least seven distinct mRNA species. To identify splice variants of BGP, antisera were raised against the A2 domain expressed in bacteria and to a peptide comprising the C-terminal 23 amino acids encoded by the 3' exon of the BGP gene. The antisera and an mAb specific for members of the BGP family were used to identify potential BGP splice variants in granulocyte membranes. For comparison, the binding of antibodies to Ag purified from human bile was investigated. In the membrane preparation from granulocytes, the only Ag identified by the mAb, the domain antiserum and the peptide antiserum, was the Ag of M(r) 160,000 recognized by a CD66 antibody. These results indicate that the M(r) 160,000 granulocyte membrane Ag of the CD66 cluster is the product of the BGP-specific mRNA containing all coding sequences of the BGP gene. Among two major biliary glycoproteins present in human bile, the M(r) 115,000 Ag contains the A2 domain, whereas the domain is lacking in the "classical" biliary glycoprotein of M(r) 85,000. None of the bile Ag bound the peptide antiserum.

The gene coding for 'biliary glycoprotein (BGP)' is a member of the carcinoembryonic antigen (CEA) gene family. A monoclonal antibody (MAb) was induced against a BGP-preparation isolated from human bile. The antibody did not crossreact with the carcinoembryonic antigen (CEA) and different non-specific crossreacting antigens. The anti-BGP MAb was used to identify BGP-related antigens in membrane extracts from granulocytes and the colonic carcinoma cell line HT-29. In granulocyte membranes, a single antigen of Mr 160,000 was bound. In membranes from HT-29 cells, a main antigen of Mr 85,000 was present. At high antigen concentration, an additional antigen of Mr 115,000 was identified. Since several transcripts of the BGP gene have been identified, the different BGP related antigens are probably products of alternatively spliced mRNAs.