Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and metastases. Human mucins are derived from a heterogeneous family of genes, labeled MUC1-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens. Probes and antibodies for specific mucin tandem repeat sequences were used for RNA and immunohistochemical analysis. Normal stomach mucosa was characterized by expression of MUC1, MUC5, and MUC6 mRNA and immunoreactive protein, without MUC2, MUC3, and MUC4 gene expression. In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metaplasia. Gastric cancers exhibited markedly altered secretory mucin mRNA levels compared with adjacent normal mucosa, with decreased levels of MUC5 and MUC6 mRNA and increased levels of MUC3 and MUC4 mRNA. Overall, immunoreactive MUC1 mucin was detected in 72% of 33 gastric cancers, and secretory mucin core peptides were expressed in 34% (MUC2), 45% (MUC3), 19% (MUC5), and 57% (MUC6) of these specimens. Coexpression of multiple (three or more) mucin core proteins occurred in 15 of 25 (60%) advanced (stages III and IV) cancers compared with 1 of 8 (12.5%) early (stages I and II) cancers (P < 0.048). We conclude that human gastric epithelium has a unique mucin gene pattern, which becomes markedly altered in preneoplastic and neoplastic specimens. Increased mucin gene heterogeneity in gastric adenocarcinomas is associated with advanced cancer stage.
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PMID:Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. 778 Sep 85

Ovarian cancer is a highly lethal disease with metastases present in the majority of patients at the time of diagnosis. The molecular mechanisms underlying the metastatic process of this cancer are not well understood. One family of cell-associated and secreted glycoproteins, the mucin glycoproteins, has been implicated in events leading to metastasis of several epithelial cancers including gastrointestinal and lung cancers. The purpose of this study was to characterize mucin gene expression in ovarian cancers and relate expression to tumor histology, stage, and patient survival. RNA was isolated from 29 epithelial ovarian cancers, 1 neuroendocrine carcinoma, 3 mixed mesodermal tumors, and two transformed, yet nonmalignant, ovarian epithelial cell lines. The expression of mucin genes, MUC1, 2, 3, 4, 5AC and 5B, was determined by northern analyses. Epithelial ovarian cancers expressed several mucins including MUC1, 2, 4, and 5AC; MUC3 and 5B were rarely expressed. In contrast, the transformed nonmalignant ovarian epithelial cell lines expressed only MUC1 and 5AC. Although there was no correlation of mucin expression with tumor histology, there was a significant decrease in expression of MUC3 and MUC4 with increasing cancer stage (P < 0.05). In addition, a trend toward improved patient survival occurred with increased expression of MUC4. These observations suggest a relationship between mucin gene expression and the metastatic process in epithelial ovarian cancers. Additional investigation of MUC3 and MUC4 in ovarian cancers may lead to new approaches for early detection and therapy.
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PMID:Mucin gene expression in ovarian cancers. 985 92

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas.
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PMID:Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. 1221 83

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P<0.01) compared to the SC tumours. The MUC4 transcripts in OT tumours were very high compared to the undetectable levels in SC tumours. The SC tumour cells regained their ability to express MUC4 transcripts after in vitro culture. Immunohistochemical analysis using MUC4-specific polyclonal antiserum confirmed the results obtained by Northern blot analysis. Interestingly, the OT tumours showed expression of TGFbeta2 compared to no expression in SC, suggesting a possible link between MUC4 and TGFbeta2. The MUC4 expression, morphology, and metastasis of human pancreatic tumour cells are regulated by a local host microenvironment. TGFbeta2 may serve as an interim regulator of this function.
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PMID:MUC4 mucin expression in human pancreatic tumours is affected by organ environment: the possible role of TGFbeta2. 1476 Mar 81

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.
Cancer Metastasis Rev
PMID:Mucins and mucin binding proteins in colorectal cancer. 1500 Jan 51

The receptor tyrosine kinases (RTKs) RET, MET, and RON all carry the Met(p+1loop)-->Thr point mutation (i.e., 2B mutation), leading to the formation of tumors with high metastatic potential. Utilizing a novel antibody array, we identified constitutive phosphorylation of STAT3 in cells expressing the 2B mutation but not wild-type RET. MET or RON with the 2B mutation also constitutively phosphorylated STAT3. Members of the EPH, the only group of wild-type RTK that carry Thr(p+1loop) residue, are often expressed unexpectedly in different types of cancers. Ectopic expression of wild-type but not Thr(p+1loop)-->Met substituted EPH family members constitutively phosphorylated STAT3. In both RTK(Metp+1loop) with 2B mutation and wild-type EPH members the Thr(p+1loop) residue is required for constitutive kinase autophosphorylation and STAT3 recruitment. In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of STAT3 and elevated expression of CXCR4 was detected in metastatic thyroid C-cell carcinoma in the liver. In breast adenocarcinoma cell lines expressing multiple EPH members, STAT3 constitutively bound to the promoters of MUC1, MUC4, and MUC5B genes. Inhibiting STAT3 expression resulted in reduced expression of these metastasis-related genes and inhibited mobility. These findings provide insight into Thr(p+1loop) residue in RTK autophosphorylation and constitutive activation of STAT3 in metastatic cancer cells.
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PMID:Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells. 1548 8

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.
Clin Exp Metastasis 2005
PMID:MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer. 1647 27

Using gene expression arrays, we recently showed that MUC4 expression is significantly higher in ovarian/primary peritoneal serous carcinoma (OC/PPC) compared to diffuse peritoneal malignant mesothelioma (DMPM). In the present study, we analyzed the anatomic site-related expression of MUC4 in OC/PPC and studied its prognostic role. We additionally studied the ability of MUC4 to differentiate between OC/PPC and reactive mesothelial cells (RMC). OC/PPC effusions (n = 142) and benign reactive effusions (n = 10) were immunostained for MUC4 expression. Immunoreactivity was scored in carcinoma cells and RMC and was compared with tumor cell expression in 60 previously studied primary carcinomas and solid metastases and analyzed for association with clinicopathologic parameters, including survival. MUC4 was detected in carcinoma cells in 141/142 (99%) effusions, with comparable expression in peritoneal and pleural effusions. RMC were present in 72 malignant effusions and were MUC4-negative in all specimens, as well as in the 10 reactive effusions. MUC4 expression in carcinoma cells in effusions was significantly higher than in primary carcinomas and solid metastases (P < 0.001). Higher MUC4 expression was seen in tumors from older (>60 year) patients (P = 0.049). No association was found between MUC4 expression and other clinicopathologic parameters, including survival. MUC4 is universally expressed in OC/PPC effusions and is upregulated at this anatomic site compared to primary carcinomas and solid metastases. The data in the present study, together with our earlier report, show that MUC4 is an excellent marker for differentiating OC/PPC from both benign and malignant mesothelial cells.
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PMID:MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells. 1800 38

Peritoneal surface malignancies are characterized by the propensity for tumor growth on peritoneal surfaces without development of extraperitoneal metastases, but the molecular basis for this phenomenon is incompletely understood. Five human tumors and corresponding orthotopic animal models of human pseudomyxoma peritonei and peritoneal mucinous carcinomatosis from colorectal carcinoma were extensively characterized by immunohistochemical analysis of molecular markers of tissue differentiation (carcinoembryonal antigen, CK20, CK7, and vimentin), proliferation and metastasis (Ki-67, vascular endothelial growth factor, and S100A4), mucins (MUC1, MUC2, MUC4, MUC5AC), and adhesion molecules (E-cadherin, N-cadherin, P-cadherin, claudin 1, claudin 3, and claudin 4). Macro- and microscopic growth patterns of implanted human tissues were preserved through passages in the animals, as were with few exception immunohistochemical staining profiles, supporting the relevance of the models as tools for studying the human disease. Tissue differentiation marker expression was in accordance with previously published results and high Ki-67 score confirmed high proliferative capacity, whereas absence of metastatic capacity was supported by low expression levels of the studied metastasis markers. These mucinous tumors expressed high levels of MUC2 and MUC4, whereas MUC1 was not expressed and MUC5AC expression was variable. Similarly, specific adhesion molecules from the cadherin and claudin families were shown to be of relevance in the investigated samples. The results indicate that mucinous peritoneal surface malignancies of intestinal origin are characterized by the presence of specific molecular markers and represent a step toward understanding the complexity of this intriguing phenotypic entity.
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PMID:Exploring the peritoneal surface malignancy phenotype--a pilot immunohistochemical study of human pseudomyxoma peritonei and derived animal models. 2033 18

Cholangiocarcinoma (CC) is a highly malignant epithelial cancer of the biliary tract, the cellular and molecular pathogenesis of which remains unclear. Malignant transformation of glandular epithelial cells is associated with the altered expression of mucin. We investigated the type of mucins expressed in CC. Twenty-six patients with histologically confirmed CC were included in this study. The expression of mucin was studied by immunohistochemistry using antibodies to MUC1, MUC1 core, MUC2, MUC3, MUC4, MUC5AC, and MUC6. There was extensive (>50%) expression of mucin, mainly MUC1 in 11/25 and MUC5AC in 12/26 cases. In the case of MUC3, 6/26 cases expressed mucin extensively, whilst only 1/26 had MUC2, MUC4, and MUC6 expression. Well-differentiated tumors significantly expressed MUC3 extensively compared to poor or moderately differentiated tumors (p=0.003). Fifteen of 25 cases had metastatic disease. MUC1 was extensively expressed in 9/15 cases with metastatic disease. In contrast, MUC1 expression was present in 2/10 cases where metastases were absent. Hilar lesions were less likely to express MUC1, but this was not statistically significant. Fifteen of 25 cases had metastatic disease. Extensive MUC3 expression was significantly associated with well-differentiated tumors, whilst there was an approaching significance between the extensive expression of MUC1 and metastasis in cholangiocarcinoma.
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PMID:The expression of MUC mucin in cholangiocarcinoma. 2094 62


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