Disease relevance of CEACAM3

• Here we show that CEACAM3 can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella, and Haemophilus species [1].
• First, transfected HeLa cells expressing CEA (HeLa-CEA) and the CEA-expressing colon cancer cell line (LS 174T) bound and subsequently engulfed the Opa+ bacteria [2].
• Furthermore, OpaI E. coli directly bound purified CEA [2].
• Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpressed in many carcinomas [3].
• A cell line derived from the mouse colon adenocarcinoma, MC-38, has been transduced with a retroviral construct containing complementary DNA encoding the human carcinoembryonic antigen (CEA) gene [4].

Psychiatry related information on CEACAM3

• A consensus Development Conference was held at the National Institutes of Health from September 29-October 1, 1980, to address issues concerning the role of carcinoembryonic antigen (CEA) as a marker in the management of cancer [5].
• There is controversy, however, about the real value of CEA determinations in the clinical decision-making process and about their impact on patient prognosis [6].
• We have developed and characterized a monoclonal anti-idiotype (Id) antibody, designated 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA) and can be used as a surrogate for CEA [7].
• In the control subjects, the serum CA 195 level, unlike that of CEA, was not affected by age, gender, alcohol consumption, or tobacco use [8].
• In a Cox proportional hazards model, the TMX treatment, along with the baseline Okuda's HCC stage, the hepatitis B surface antigen, the portal vein diameter, the carcino embryonic antigen (CEA) and a self-assessment score of quality of life, were covariates predicting survival [9].

High impact information on CEACAM3

• Using a statewide cancer registry system, the analysis suggested that the preoperative level of serum CEA was an indicator of survival in patients with colorectal cancer, independent of the stage of disease at diagnosis [10].
• CEA, AFP and other potential tumor markers [11].
• We demonstrate here that CEA mediates Ca2+-independent, homotypic aggregation of cultured human colon adenocarcinoma cells (LS-180) and rodent cells transfected with functional CEA cDNA [12].
• Carcinoembryonic antigen (CEA) is a member of a family of cell surface glycoproteins that are produced in excess in essentially all human colon carcinomas and in a high proportion of carcinomas at many other sites [12].
• We also show that, whereas CEA is localized mainly to epithelial cell membranes facing the lumen in normal adult intestine, it is found on adjacent cell membranes in both embryonic intestine and colonic tumors [12].

Chemical compound and disease context of CEACAM3

• Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor [13].
• The expression of CEA and related antigens in formalin-fixed paraffin-embedded tissues of normal pancreas and different pancreatic neoplasms was studied immunocytochemically using three monoclonal antibodies (MAbs) recognizing different epitopes on CEA and related antigens [14].
• Serial plasma carcinoembryonic antigen (CEA) levels were measured in 167 patients with metastatic breast cancer treated with fluorouracil, doxorubicin hydrochloride, and cyclophosphamide (FAC) [15].
• BACKGROUND: Human carcinoembryonic antigen (CEA) is a 180-kd glycoprotein expressed in human colorectal, gastric, pancreatic, breast, and non-small-cell lung carcinomas [16].
• Combinations of serum protein-bound carbohydrates, particularly L-fucose and sialic acid, and, in addition, CEA, appear to have promise as potential biomarkers for following the course of the disease in patients with metastatic breast cancer [17].

Biological context of CEACAM3

• The granulocyte-specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM-binding pathogens that colonize human mucosal surfaces [18].
• This correlation of overproduction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation [3].
• The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage [3].
• As in humans, immune responsiveness to CEA, as reflected by antibody formation, was not detectable in transgenic mice bearing CEA-positive tumors [19].
• A 32.6-kb fragment containing the complete human CEA gene and flanking sequences was isolated from a genomic cosmid clone and used to produce transgenic C57BL/6 mice [19].

Anatomical context of CEACAM3

• Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens [1].
• We examined the role of phosphatidylinositol 3-kinases (PI3Ks) in gonococcal invasion of epithelial cell lines expressing either CEACAM1 or CEACAM3 [20].
• Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine-based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors [13].
• In addition, although CEACAM3 is not recognized as a receptor by the subfamily of Afa/Dr adhesins, it is recruited around bacteria in HeLa cells [21].
• CEA was not found by immunohistochemistry in other tissues of the digestive tract, nor was it found in a wide range of other tissues or organs [19].

Associations of CEACAM3 with chemical compounds

• Internalization and Rac stimulation are also inhibited by compromising the integrity of an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence in the cytoplasmic tail of CEACAM3 or by interference with Src family protein tyrosine kinases that phosphorylate CEACAM3 [1].
• CEACAM3-mediated internalization, but not that mediated by CEACAM1, was accompanied by localized and transient accumulation of the class I PI3K product phosphatidylinositol 3,4,5-trisphosphate at sites of bacterial engulfment [20].
• These interactions were inhibited by anti-CEA antibody, but could not be inhibited by addition of heparin [2].
• Incorporation of fucose and galactose into purified carcinoembryonic antigen (CEA), used as an exogenous acceptor by colon glycosyltransferases, was demonstrated by immunoprecipitation with rabbit antiserum to human CEA [22].
• The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin superfamily and can be subdivided into the CEA and pregnancy-specific glycoprotein subgroups [23].

Physical interactions of CEACAM3

• Moreover, CEACAM3 engagement triggers membrane recruitment and increased GTP loading of Rac that are not observed upon bacterial binding to CEACAM6 [1].

Regulatory relationships of CEACAM3

• CEACAM3 was tyrosine phosphorylated by a Src family kinase-dependent process upon infection by gonococci expressing CEACAM-specific Opa proteins [13].

Other interactions of CEACAM3

• CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative versions of the small GTPase Rac [1].
• Genomic organization, splice variants and expression of CGM1, a CD66-related member of the carcinoembryonic antigen gene family [24].
• In vitro exposure of acute promyelocytic leukemia cells to arsenic trioxide (As2O3) induces the solitary expression of CD66c (NCA-50/90), a member of the CEA family [25].
• On the basis of previous work with various monoclonal antibodies (Mab) raised against carcino-embryonic antigen (CEA), the anti-CEA Mab 47 was identified which selectively reacted with a surface glycoprotein (95 kDa; NCA 95) of normal human granulocytes [26].
• Many polyps and dysplastic lesions in ulcerative colitis have phenotypic changes (blood group antigen, cytokeratins, CEA, TAG-72.3 antigen expression) and genetic changes (c-K-ras mutation, enhanced c-myc expression and pp60c-src activity) which are characteristic of invasive cancers [27].

Analytical, diagnostic and therapeutic context of CEACAM3

• Extreme heterogeneity was observed both by radioimmunoassay and immunohistochemical procedures for the expression of carcinoembryonic antigen (CEA), colon-specific antigens (CSAp), and colonic mucin antigen (CMA) within the tumors [28].
• Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft [29].
• Thus, CEA transgenic mice may serve as a useful model for studying the efficacy and safety of various immunotherapy strategies directed at this tumor self-antigen [19].
• IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations [30].
• This antibody has been examined for its usefulness in detecting CEA in suspension and has been found to work both in sandwich enzyme-linked immunosorbent assays and in sandwich radioimmune assays [31].

References