Disease relevance of CEACAM6

• Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance [1].
• Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors [1].
• CEACAM6 revealed a broader expression zone in proliferating cells in hyperplastic polyps and adenomas compared with normal mucosa, whereas CEACAM7 was completely absent [2].
• The results demonstrate that only E. coli expressing a subfamily of Afa/Dr adhesins, named here Afa/Dr-I, including Dr, F1845 and AfaE-III adhesins, bound onto CHO cells expressing CEACAM1, CEA or CEACAM6 [3].
• This novel mouse will ensure better assessment than previously utilized models for the preclinical testing of CEA-targeted therapies and perhaps allow the testing of CEACAM6, which is overexpressed in many solid tumors and leukemias, as a therapeutic target [4].

Psychiatry related information on CEACAM6

• All-night polysomnographic recordings of 10 JME patients were analyzed for variations of epileptiform EEG abnormalities in relation to sleep stages and to different microstructural variables (NCAP, CAP, phases A and B) [5].
• Because panic disorder is highly disabling but responds well to psychological and pharmacologic treatments, screening NCA patients in the cardiology population for this disorder is recommended [6].
• Statistical comparison between CAP and NCAP epochs revealed a significant difference for most of the frequency domain parameters (increase of the low-frequency band, increase of the low-frequency/high-frequency ratio and decrease in the high-frequency band during CAP) both in Stage 2 and in slow-wave sleep [7].
• The objective of the current study was to compare psychosocial factors, clinical pain, and responses to experimental pain in NCA patients, patients with ischemic heart disease (IHD), and healthy control subjects [8].
• Other diagnostic instruments exist which accomplish the same diagnostic task as the NCA diagnostic criteria, but in addition have more desirable psychometric qualities and are more utilitarian [9].

High impact information on CEACAM6

• Moreover, CEACAM3 engagement triggers membrane recruitment and increased GTP loading of Rac that are not observed upon bacterial binding to CEACAM6 [10].
• The ability to mediate invasion of the transfectant cells was (CGM1a >CEA >BGPa >NCA >CGM6 = Neo) [11].
• The following antigenic systems were found in lung cancers: a) antigens specific for most squamous cell cancers and adenocarcinomas, which are undetectable in small cell cancers; b) NCA-type antigens; c) CEA-like antigens; and d) the antigen responsible for alpha-1-antichymotrypsin reactivity [12].
• A simultaneous production of nonspecific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) by the same individual cells of an established human pancreatic cell line (QGP-1) was demonstrated by the immunoperoxidase method [13].
• Kinetics of cell proliferation and production of CEA and NCA were analyzed, and active synthesis of both antigens was found to be accompanied with the active proliferation of cultured cells [13].

Chemical compound and disease context of CEACAM6

• CEACAM6 is a potential prognostic indicator and potential chemoresistant marker to gemcitabine for patients with intrahepatic cholangiocarcinoma [14].
• c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components [15].
• The 95-kilodalton membrane glycoprotein overexpressed in novel multidrug-resistant breast cancer cells is NCA, the nonspecific cross-reacting antigen of carcinoembryonic antigen [16].
• We have previously described a recombinant baculovirus BVCEA-140 expressing the full-length human CEA and a variant, BVCEA-16, that encodes only the NH2-terminal domain, as well as a recombinant (BVNCA) expressing the closely related molecule nonspecific cross-reactive antigen (NCA) [17].
• From inhibition studies with aromatic mannose compounds, it was suggested that in contrast to Salmonella strains E. coli strains exhibit a higher hydrophobicity in the binding region adjacent to the CEA-, NCA- and BGP-binding site [18].

Biological context of CEACAM6

• CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups [1].
• CEACAM6 and CEACAM7 expression correlated with apoptosis at the table region of the normal colon, and both were absent from highly proliferating cells at the base of colonic crypts [2].
• Thus, deregulated expression of CEA/CEACAM6 could directly contribute to colon tumorigenesis by the inhibition of terminal differentiation and anoikis [19].
• Our data show that both the CEA and NCA polypeptides are organized into extracellular domains, some with cysteine-linked loops, that share extensive sequence homology (approximately 78% overall) with each other and appear similar to immunoglobulin superfamily members [20].
• Stable overexpression of CEACAM6 in Capan2 increased gemcitabine chemoresistance, whereas CEACAM6 gene silencing in BxPC3 markedly increased the sensitivity of these cells to gemcitabine [21].

Anatomical context of CEACAM6

• For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen-directed reorganization of the actin cytoskeleton is not required [22].
• CEACAM6 was expressed in granulocytes and epithelia from various organs [2].
• Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8 [23].
• We report here the direct effects of deregulated overexpression of CEA/CEACAM6, at levels observed in colorectal carcinomas, on the differentiation of two human colonic cell lines, SW-1222 and Caco-2 [19].
• In ALLs of B-cell origin, 82% of the samples expressed at least one CEA subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both [24].

Associations of CEACAM6 with chemical compounds

• CEA and NCA mRNAs were clearly detectable in the cytoplasm of columnar and goblet cells at the free luminal surface and the upper crypts with low hybridization in the mid crypt and the crypt base [25].
• The purpose of this study was to determine the role of CEACAM6 in cellular chemoresistance to gemcitabine [21].
• Using confocal microscopy and specific antibodies, CEA and CEACAM6 were demonstrated to co-cluster with integrin alpha5beta1 on the cell surface [26].
• Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein [27].
• As controls fluorescein-labelled CEA and NCA were used [28].
• Our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-gamma or TNF-alpha stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients [29].

Regulatory relationships of CEACAM6

• The NH(2)-terminal domain (N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell [23].
• In contrast, after in vitro stimulation of peripheral blood PMN with phorbol myristate acetate, CD66c was much less up-regulated compared with CD66a and CD66b [30].
• IFN-gamma induced NCA mRNA in three of four cell lines tested [31].
• Immunological similarity of NCA (non-specific cross-reacting antigen) in feces with alpha 1-acid glycoprotein [32].

Other interactions of CEACAM6

• CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative versions of the small GTPase Rac [10].
• In this study we demonstrate that CEACAM1 interacts with CEACAM5, but not with CEACAM6 [33].
• We compared the expression patterns of CEACAM1-L, CEACAM1-S, CEACAM6, and CEACAM8 in purified populations of neutrophilic granulocytes, B lymphocytes, and T lymphocytes from rats, mice, and humans [34].
• We have now carried out immunohistochemical expression studies on 35 different organs, using CEACAM6-specific (9A6) and CEACAM7-specific (BAC2) monoclonal antibodies [2].
• Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12 [35].

Analytical, diagnostic and therapeutic context of CEACAM6

• Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear [1].
• Although opposite has previously been suggested, we show that CEACAM6 transcription is invariably followed by surface expression (by quantitative RT-PCR on sorted cells) and that malignant cells containing CD66c in cytoplasm without surface expression are not found by flow cytometry nor by Western blot in vivo [36].
• SDS-PAGE analysis of immunoprecipitates from the granules revealed that NCA-95 (CD66c, NCA-50/90) exists predominantly in the azurophil granule-enriched fraction [37].
• METHODS: CEACAM6 expression was quantified by real-time polymerase chain reaction (PCR) and Western blot [38].
• Interestingly, patients with high CEACAM6 expression showed a significantly poorer disease-free survival rate than those with low CEACAM6 expression [14].

References