Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We established a model of orthotopic injection of a syngeneic pancreatic tumor cell line in C57BL/6 mice and evaluated the effects of organ site on induction of immunity to a tumor-specific antigen, MUC1. Mice were challenged with a syngeneic pancreatic adenocarcinoma cell line that expressed MUC1 (Panc02-MUC1) by orthotopic injection into the pancreas, or by subcutaneous injection. Tumor cells injected into the pancreas grew much faster than those injected subcutaneously. Mice challenged subcutaneously with Panc02-MUC1 rejected tumors or developed slowly growing tumors that were negative for MUC1 expression. In contrast, mice challenged orthotopically into the pancreas developed progressive tumors that were positive for MUC1 expression. Sera from mice that rejected PancO2-MUC1 (tumor-immune mice) showed no detectable IgG1 and IgM titers against the MUC1 tandem-repeat peptide, whereas mice with progressive tumor growth had significant titers of IgG1 and IgM specific for MUC1. This suggests that the humoral immune response was ineffective in mediating tumor rejection. The results show that the growth properties and immunological rejection of pancreatic tumors is affected by the organ site at which the tumor grows.
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PMID:Organ-specific pancreatic tumor growth properties and tumor immunity. 1002 73

Adenocarcinomas of glandular tissues produce a hypoglycosylated form of a normal glycoprotein (mucin) that elicits an immune response. A tumor-specific epitope of mucin occurs in a 20-amino-acid, tandemly repeated domain of human MUC1 mucin. A synthetic gene encoding five tandem repeats of the tumor-specific epitope of human mucin (m5tr) was designed for efficient cloning and expression in Escherichia coli for subsequent use in preparing reagent quantities of the mucin 5 tandem repeat (mtr5) polypeptide. The synthetic gene was cloned in the correct reading frame into the maltose-binding protein (MBP) fusion expression vector pMAL-p2. Bacterial clones containing the mucin synthetic gene (m5tr) were shown to produce the intended recombinant fusion protein, MBP-mtr5. The fusion protein represents a significant fraction of the cell protein, 50% or more of which is secreted into the periplasm. The MBP-mtr5 protein is largely intact and easily prepared in sufficient quantity and purity for preliminary structure-function studies.
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PMID:Design and expression of a synthetic mucin gene fragment in Escherichia coli. 1002 81

As recently reported, DF3/MUC-1 molecules having cytokine receptor-like sequences (CRL) at the extracellular region, are likely to function in signal transduction pathways. To elucidate the functional significance of CRL expressed on the DF3/MUC1 molecule, immunohistochemical localization of CRL and/or DF3 was investigated in cases of 115 patients with gastric carcinomas, treated by surgical resection. CRL was detected in 65 of 115 patients (56.5%), DF3 in 85 (73.9%), and both DF3 and CRL in 52 (45.2%). The combined immunohistochemical analysis of CRL and/or DF3, revealed that simultaneous expression of DF3 and CRL (DF3+/CRL+) significantly correlated to lymph node metastasis and to blood vessel invasion, and that patients with DF3+/CRL+-tumors survived for a significantly shorter period after surgery than did the other three groups (DF3+/CRL-, DF3-/CRL+, and DF3-/CRL-). Multivariate analysis showed independent prognostic significance for DF3+/CRL+ expression (hazard ratio [HR]=2.733, P=0.0085), and surgical cure (HR=4.334, P=0.003). To investigate the biological role of the simultaneous expression of DF3 and CRL, we constructed DF3-/CRL+ (NR-MC-38) and DF3+/CRL+ (R-MC-38) cells by transducing a mouse colon adenocarcinoma cell line MC-38 expressing neither DF3 nor CRL with MUC-1 cDNA containing ten tandem repeats (R-MC-38) or MUC-1 cDNA devoid of tandem repeats (NR-MC-38). R-MC-38 (DF3+/CRL+) cells were more invasive than NR-MC-38 (DF3-/CRL+) and MC-38 (DF3-/CRL-) cells. When these transfectants were incubated with pAb CRL, the invasiveness of R-MC-38 (DF3+/CRL+) was strikingly elevated over the case with native MC-38 (DF3-/CRL-) and NR-MC-38 (DF3-/CRL+) cells. The pAb CRL-induced invasiveness of R-MC-38 cells was inhibited by adding mAb DF3 or CRL peptides together with pAb CRL. These results suggest that an expression of DF3/MUC1 is highly associated with cell-invasiveness, and the DF3/MUC1-associated invasiveness is amplified by CRL. Thus DF3+/CRL+-MUC-1 molecule seems to be closely involved in a poor prognosis for gastric cancer patients.
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PMID:Prognostic values of MUC-1 molecule expressing cytokine receptor-like epitope and DF3 in patients with gastric carcinoma. 1002 73

The levels of mRNA corresponding to the MUC1, MUC2, MUC5AC, MUC5B, and MUC6 genes were determined in 19 human colon adenocarcinoma cell lines by the reverse transcriptase-polymerase chain reaction method using specific primers in an attempt to correlate to the levels of cell surface carbohydrate epitopes. All 19 cell lines expressed MUC1 and MUC5B mRNA, whereas MUC2, MUC5AC, or MUC6 mRNA were only detected in 8, 3, or 2 of 19 cell lines, respectively. Sialyl Lewis a carbohydrates, identified by the monoclonal antibody (mAb) CA19-9, and sialyl Lewis X carbohydrates. identified by mAb KM93, were observed, with most of the cell lines expressing multiple mucin core polypeptide genes but with few cell lines expressing only MUC1 and MUC5B. Sialyl Tn epitopes identified by mAb B195.3R11 and by mAb TKH-2 were strongly expressed on both of two MUC6-positive cells, whereas only a small portion of MUC6-negative cells expressed these epitopes. Strict correlation between mucin gene expression and any carbohydrate epitopes examined was not observed.
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PMID:Expression of mucin genes and carbohydrate epitopes in 19 human colon carcinoma cell lines. 1010 Jul 57

At least seven human mucin genes have been described, which express glycoproteins MUC1-7 in various tissues. It has been shown that different mucins are expressed in various gastric disease states compared to the normal. In this study we used histochemical and immunohistochemical methods to determine the type and pattern of mucin in 54 patients with a variety of gastric conditions [i.e., normal controls, fetal stomachs, gastritis, low-grade dysplasia, intestinal metaplasia (associated with gastritis, benign ulcers, dysplasia, and cancer), early and advanced intestinal type adenocarcinoma, and diffuse adenocarcinoma]. We report for the first time the use of all seven MUC antibodies in the various conditions. Normal controls were immunoreactive for MUC4, 5, and 6 , and gastritis specimens showed similar results, although the latter showed more MUC1 immunoreactivity. Whereas early fetal stomach showed no MUC immunoreactivity, MUC4, 5, and 6 were present from the early second trimester onwards. There was no significant difference between dysplasia and intestinal metaplasia, both categories showing the presence of MUC2 and 3 predominantly. Early intestinal type adenocarcinomas did not show any mucins in the majority of cases. Advanced intestinal type adenocarcinomas showed immunoreactivity predominantly for MUC1, 5, and 6, as well as MUC2 in some cases. Diffuse adenocarcinomas showed strong positive MUC2 and 6 staining, and in some cases MUC5 and 7. In conclusion, we have shown different patterns of mucin immunoreactivity in various gastric disease states. Specimens with dysplasia, intestinal metaplasia, late intestinal type adenocarcinoma, and diffuse gastric cancer were characterized by increased diversity of mucin types, whereas early intestinal cancer showed loss of mucin immunoreactivity.
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PMID:Immunohistochemical detection of gastric mucin in normal and disease states. 1022 22

Expression of mucin core protein MUC1 and MUC2 was examined at the protein and mRNA level in 55 cases of carcinoma and 20 of dysplasia, and in 15 non-dysplastic epithelia of the gall bladder. In non-dysplastic epithelium, MUC1 protein was not expressed, while in dysplasia, MUC1 was focally expressed in ten cases, particularly in those associated with carcinoma. In carcinoma, MUC1 was expressed heterogeneously, and the frequency and extent of MUC1 expression increased with histological dedifferentiation. MUC1 was found on the apical cell surface and also in the cytoplasm in well- and moderately-differentiated carcinoma, and on the cell border in poorly-differentiated cases. In infiltrative regions, MUC1 expression was more predominant and MUC1 frequently leaked outside the foci of carcinoma. By contrast, MUC2 was focally expressed in non-dysplastic as well as in dysplastic epithelia and more frequently in well-differentiated adenocarcinoma. MUC2-positive cells resembled goblet cells, whether in non-dysplastic epithelium, dysplasia or carcinoma. Cell proliferative activity was higher in MUC1-positive than in MUC1-negative carcinoma cells. Distributions of MUC1 and MUC2 mRNA signals and of MUC1 and MUC2 proteins were similar in carcinoma and dysplasia. These results suggest that MUC1 expression by gall bladder carcinoma may reflect histological dedifferentiation, increased proliferative activity, and invasiveness, while MUC2 expression is related to lower proliferative activity and reflects some differentiation towards goblet cells; and that MUC1 expression in gall bladder dysplasia reflects malignant transformation.
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PMID:Expression of MUC1 and MUC2 mucin core proteins and their messenger RNA in gall bladder carcinoma: an immunohistochemical and in situ hybridization study. 1039 37

Many tumor-associated epitopes possess carbohydrate as a key component, and thus changes in the activity of glycosyltransferases could play a role in generating these epitopes. In this report we describe the stable transfection of a human pancreatic adenocarcinoma cell line, Panc1-MUC1, with the cDNA for mucin core 2 GlcNAc-transferase (C2GnT), which creates the core 2 beta-1,6 branch in mucin-type glycans. These cells lack endogenous C2GnT activity but express a recombinant human MUC1 cDNA. C2GnT-transfected clones expressing different levels of C2GnT were characterized using monoclonal antibodies CC49, CSLEX-1, and SM-3, which recognize tumor-associated epitopes. Increased C2GnT expression led to greatly diminished expression of the CC49 epitope, which we identified as NeuAcalpha2,6(Galbeta1,3)GalNAcalpha-Ser/Thr in the Panc1-MUC1 cells. This was accompanied by the emergence of the CSLEX-1 epitope, sialyl Lewis x (NeuAcalpha2,3Galbeta1,4(Fucalpha1,3)GlcNAc-R), an important selectin ligand. Despite this, however, the C2GnT transfectants could not bind to selectins. Increased C2GnT expression also led to masking of the SM-3 peptide epitope, which persisted after the removal of sialic acid, further suggesting greater complexity of the core 2-associated O-glycans on MUC1. The results of this study suggest that C2GnT could play a regulatory role in the expression of certain tumor-associated epitopes.
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PMID:Expression of core 2 beta-1,6-N-acetylglucosaminyltransferase in a human pancreatic cancer cell line results in altered expression of MUC1 tumor-associated epitopes. 1045 30

The morphology, cell growth, antigenic expression and tumorigenicity of cell subpopulations from the A549 lung adenocarcinoma isolated by Percoll gradient separation have been analysed. Four subpopulations were obtained (subpopulations A, B, C and D). Immunocytochemical analysis of several antigens was performed with monoclonal antibodies (MAbs): MUC1 mucin (C595, HMFG1 and HMFG2), MUC5B (PANH2); gp230 (PANH4); carbohydrate antigens including sialyl Lewis x (KM93), Tn antigen (83D4), Lewis y (C14); 5, 6, 8, 17 and 19 cytokeratins and p53. The cell population D tended to form cell aggregates that piled up on the monolayer similar to overgrowth cultures of the A549 parental cell line, whereas A, B and C cell subpopulations formed well spread monolayers. Both parental A549 and subpopulation D secreted abundant mucus. The topographic distribution and secretion production were correlated with tumorigenic assays since only subpopulation D grew in nude mice exhibiting reduced latency period; these characteristics correlated with the fast growth of the subpopulation D in vitro. Immunocytochemical analysis demonstrated that subpopulation D showed greater expression of MUC1 mucin and carbohydrate antigens such as Tn antigen, sialyl Lewis x and Lewis y and less expression of cytokeratins, p53, MUC5B and gp230; conversely, subpopulations A, B and C showed the opposite antigenic profile. Our results illustrate heterogeneity in the A549 cell line; subpopulations A, B and C retained characteristics of more differentiated adenocarcinoma while subpopulation D displayed features of a less differentiated tumor line.
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PMID:Identification and characterization of different subpopulations in a human lung adenocarcinoma cell line (A549). 1049 Oct 17

Ovarian carcinomas are known to be diverse in their histological types and response to therapeutic agents. Specific immunotherapy by the use of mucins or carbohydrate vaccines has been attempted, in which expression of these epitopes by each histotype should clearly be assessed. Seventeen human ovarian carcinoma cell lines were evaluated for their expression of mucin core polypeptide mRNAs (MUC1, MUC2, MUC3, MUC5AC, MUC5B, and MUC6) by the reverse transcription-polymerase chain reaction. They were also examined for their expression of mucin-associated carbohydrate epitopes by flow cytometry. Eleven monoclonal antibodies, including those specific for Lewis antigen-related epitopes and Tn-related epitopes, were used. Expression of the MUC1 gene and sialyl Lewis X was characteristic to all five cell lines derived from clear cell adenocarcinomas. Multiple mucin genes and a diverse range of carbohydrate epitopes were observed with all six cell lines derived from mucinous adenocarcinomas. Mucin-associated carbohydrate epitopes were not detected on three of four serous adenocarcinoma cell lines, although MUC1 and MUC2 mRNAs were detected in all of them. Therefore, ovarian carcinoma cells from tumors of different histological types showed characteristic expression patterns of mucin genes and carbohydrate epitopes.
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PMID:Carbohydrate epitopes and mucins expressed by 17 human ovarian carcinoma cell lines. 1060 18

MUC1 mucin is a target protein for many monoclonal antibodies. Human MUC1 detected by a murine anti-KL-6 monoclonal antibody that recognizes a sialylated carbohydrate chain has been designated KL-6/MUC1. Given the heterogeneous antigenicity of KL-6/MUC1, we established a new murine monoclonal antibody, H9, that reacts with epitope DTRP (Asp-Thr-Arg-Pro) peptides within the immunodominant region of the tandem repeat of MUC1 mucin. The reactivity of the H9 antibody differs from that of other previously reported antibodies that recognize the tandem repeat region of MUC1. Immunohistochemical experiments indicate that the reactivity of the H9 antibody is similar to that of other antibodies directed against MUC1 core proteins. A new cancer-associated protein detected by a sandwich assay using the H9 antibody as a catcher and the KL-6 antibody as a tracer is designated HK9. Serum HK9 levels showed a high expression level in lung cancer: 51% (19/37 cases) for adenocarcinoma, 39% (11/28 cases) for squamous cell carcinoma, and 67% (10/15 cases) for small cell carcinoma. The HK9 expression in lung cancer increased with cancer progression. These findings suggest monoclonal antibody H9 to be a novel antibody that reacts with an epitope within the tandem repeat region of MUC1, and that the cancer-associated antigen HK9 may have useful tumor-associated properties.
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PMID:A novel monoclonal antibody, H9, directed against the core protein of MUC1 mucin. 1067 62


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