Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.
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PMID:Phenotypic alterations of mucins and cytokeratins during gallbladder carcinogenesis. 1526 Aug 48

Mucins represent a family of glycoproteins characterized by repeat domains and a dense O-glycosylation. During the last two decades, the gene and peptide structures of various mucins as well as their glycosylation states were partly elucidated. Characteristic tumor-associated alterations of the expression patterns and glycosylation profiles were observed in biochemical, immunochemical, and histological studies and are discussed in the light of efforts to use the most prominent member in this family, MUC1, as a tumor target in anti-tumor strategies. Within this context the present review, focusing on MUC1, describes recent work on the regulation of mucin biosynthesis by cytokines and hormones, the role of mucins in cell adhesion, and their interaction with the immune system. Important aspects of clinical diagnostics based on mucin antigens are discussed, including the application of tumor serum assays and the significance of numerous studies revealing correlations between the expression of peptide cores or mucin-associated carbohydrates and clinicopathological parameters like tumor progression and prognosis.
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PMID:MUC1 and the MUCs: a family of human mucins with impact in cancer biology. 1527 May 54

Intraductal papillary-mucinous tumor of the pancreas is occasionally accompanied by biliopancreatic fistula. However, it is difficult to show the inflow of mucin produced by the tumor into the common bile duct. To confirm the biliopancreatic fistula, the mucin-rich fraction was purified from the bile and stained with antimucin antibodies. Western blot analysis showed characteristic smear staining patterns for mucin molecules with three types of antimucin antibodies. Immunohistochemical analysis with the antibody showed significant signals of the cancer cells and the luminal content of the dilated pancreatic duct. These results showed that the bile contained an abundance of mucin, which was produced by the primary pancreatic tumor. In cases with intraductal papillary-mucinous tumor of the pancreas, biochemical analysis of mucin molecules in the bile can be of clinical use in consideration of pathological process of tumor progression.
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PMID:Biliopancreatic fistula caused by an intraductal papillary-mucinous tumor of the pancreas confirmed by biochemical analysis of mucin. 1536 42

CD97, a membrane protein expressed at high levels on inflammatory cells and some carcinomas, is a member of the adhesion G protein-coupled receptor family, whose members have bipartite structures consisting of an extracellular peptide containing adhesion motifs noncovalently coupled to a class B 7-transmembrane domain. CD97alpha, the extracellular domain of CD97, contains 3 to 5 fibrillin class 1 epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) tripeptide, and a mucin stalk. We show here that CD97alpha promotes angiogenesis in vivo as demonstrated with purified protein in a directed in vivo angiogenesis assay (DIVAA) and by enhanced vascularization of developing tumors expressing CD97. These data suggest that CD97 can contribute to angiogenesis associated with inflammation and tumor progression. Strong integrin alpha5beta1 interactions with CD97 have been identified, but alpha v beta3 also contributes to cell attachment. Furthermore, soluble CD97 acts as a potent chemoattractant for migration and invasion of human umbilical vein endothelial cells (HUVECs), and this function is integrin dependent. CD97 EGF-like repeat 4 is known to bind chondroitin sulfate. It was found that coengagement of alpha5beta1 and chondroitotin sulfate proteoglycan by CD97 synergistically initiates endothelial cell invasion. Integrin alpha5beta1 is the first high-affinity cellular counterreceptor that has been identified for a member within this family of adhesion receptors.
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PMID:CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. 1557 72

The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers.
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PMID:Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. 1574 2

Mucins are glycoproteins normally synthesized by a variety of secretory epithelial cells. The aim of this study was to investigate the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUCB, MUC6, MUC7) in mucoepidermoid carcinomas, the most frequent malignant tumor of salivary glands. Forty mucoepidermoid carcinomas and twenty-two normal salivary glands were studied for these mucins by immunohistochemistry from formalin-fixed and paraffin-embedded material. Normal salivary glands frequently expressed MUC1 and MUC4, mainly in ductal cells; MUC5B and MUC7 stained mucous and serous acini respectively of submandibular and minor salivary glands; and MUC5AC and MUC2 were poorly detected in excretory ducts. All mucoepidermoid carcinomas expressed MUC1, and 38/40 tumors expressed MUC4. Both membrane-bound mucins stained membranes and cytoplasm of all cell types (epidermoid, intermediate, mucous, clear and columnar). MUC5AC and MUC5B stained glandular differentiated cells in most tumors (29/40 and 33/40 cases, respectively). MUC6 was positive in 13/40 tumors, and both MUC2 and MUC7 in only 2/40 tumors. The high expression of MUC1 was related to high histologic grades, high recurrence and metastasis rates and a shorter disease-free interval (P < 0.05). Conversely, MUC4 high expression was mainly related to low-grade tumors, lower recurrence rates and a longer disease-free interval (P < 0.05). In conclusion, mucoepidermoid carcinomas of salivary glands usually express MUC1, MUC4, MUC5AC and MUC5B; less frequently MUC6; and rarely MUC2 and MUC7. This mucin expression pattern can be useful for diagnostic purposes. Therefore, MUC1 expression is related to tumor progression and worse prognosis, whereas MUC4 expression is related to a better prognosis.
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PMID:Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands. 1589 48

Malignant transformation of ovarian cells of surface epithelial origin is associated with expression of a membrane-spanning glycoprotein, cancer antigen (CA)-125. The bulk of the putative CA-125 molecule is comprised a very large, folded, multivalent, mucin-like exodomain. That the extracellular motif of CA-125 exerts immunosuppressive effects which promote tumor progression has been suggested. We report that CA-125 attenuates complement lysis of antibody-sensitized cells. The secreted form of CA-125 derived from culture medium of the human ovarian adenocarcinoma cell line OVCAR-3 caused a dose-response inhibition of sheep erythrocyte hemolysis. Moreover, OVCAR-3 cells became prone to complement attack (trypan blue uptake) mediated by a gonadotropin-releasing hormone receptor antibody when (membrane-bound) CA-125 was excised/removed by trypsin/washing; this effect was counteracted by replacement with (soluble) CA-125. It is conceivable that CA-125 entraps/sheds effectors of the complement cascade.
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PMID:Complement-inhibiting effect of ovarian cancer antigen CA-125. 1598 25

Trefoil factor family (TFF) of proteins are involved in mucosal protection and healing and are induced in inflammatory diseases and neoplastic progression. The purpose of this investigation was to determine if expression of the trefoil factor family (TFF) proteins is altered in human pterygium compared to in normal conjunctiva. Fourteen pterygia (P) and 21 biopsies from normal human conjunctiva (NC) were studied. TFF1, TFF2 and TFF3 mRNA levels were measured by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR), and TFF1 mRNA levels in addition by real-time PCR. The cellular expression of TFF1 (pS2), TFF3 (intestinal trefoil factor) and M1/MUC5AC mucin in ten pterygia and ten normal human conjunctiva specimens was analyzed by immunohistochemistry using specific monoclonal antibodies. TFF1 mRNA levels were higher in P than in NC (p=0.02). Accordingly, intensity of TFF1 and mucin MUC5AC immunostaining was higher in P than in NC. Mucus-secreting goblet cells (GC) were more densely packed in P than in NC. In both cases, TFF1 protein was detected in GC only, but was not systematically expressed in all GC. In addition, TFF3 mRNA levels were similar (p=0.89) in NC and P, while TFF2 (spasmolytic polypeptide) mRNA were not detected. Both TFF3 and MUC5AC proteins were clearly detected in all GC identified in NC and P. Increased expression of TFF1 mRNA and protein is observed in pterygium GC, suggesting that this trefoil protein might exert protective and beneficial roles during the pathogenesis of this benign and inflammatory conjunctival tumor.
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PMID:Trefoil factor family mRNA and protein expression in pterygium. 1614 16

MUC1 represents a promising marker in breast cancer. However, due to the structural complexity of the MUC1 glycoprotein, multiple epitopes can be detected by monoclonal antibodies. This fact may be responsible for the contradictory results of previous investigations regarding the clinical and prognostic relevance of MUC1 expression in breast cancer. Therefore, we tried to evaluate the role of different glycosylated and non-glycoslyated MUC1 epitopes as well as other mucin-associated peptides (MUC2) and carbohydrates (Thomsen-Friedenreich antigen, sialyl-Lewisa, sialyl-Lewisx) as predictors of the clinical course and prognosis in mammary carcinomas. An immunohistochemical study applying numerous monoclonal antibodies (mabs) was performed to characterize the expression of a selected panel of MUC1 epitopes, and of MUC2, Thomsen-Friedenreich antigen, sialyl-Lewisa, and sialyl-Lewisx in a series of 140 patients with breast cancer. The results were correlated with clinicopathological variables as well as overall survival. Generally, more than 90% of the mammary cancers, were strongly stained with the MUC1-specific mabs. Especially ductal and lobular carcinomas were strongly MUC1- and sialyl Lewisa-positive, whereas MUC2 binding was significantly elevated in mucinous neoplasms. Associations between the immunoreactivity of any mab under study and tumor progression as reflected by pTNM staging could not be observed. However, expression of the sialylated MUC1 epitope detected by mab MY1.E12 was revealed as a favourable independent prognostic factor. These results confirm that MUC1 is generally strongly expressed in mammary carcinomas. As an exception, mucinous carcinomas are significantly less MUC1 reactive, but strongly express MUC2. Our data suggest that only the presence of a sialylated short-chain MUC1 glycoform is associated with a better prognosis, whereas the other molecules under study are not correlated with the course of disease and survival probability.
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PMID:Expression of MUC1, MUC2 and oligosaccharide epitopes in breast cancer: prognostic significance of a sialylated MUC1 epitope. 1621 Dec 24

A therapeutic approach being investigated for a variety of pathologies is tissue regeneration using a patient's own cells. Such studies have been hampered due to the difficulty in growing epithelial cells for prolonged periods in culture. Replicative senescence due to short telomeres and p16 induced by culture stress work together to inhibit cell growth. Forced expression of telomerase (hTERT) can prevent replicative senescence, and expression of the cell cycle protein cdk4 can sequester p16, thereby immortalizing epithelial cells in culture. In the present study, we used this method to immortalize human bronchial epithelial cells (HBECs) to determine whether immortalized HBECs retain the ability to differentiate normally. HBECs were plated atop contracted collagen gels containing lung fibroblasts. This three-dimensional (3D) tissue model was cultured initially submerged, then raised to the air/liquid interface for up to 28 days. Normal differentiation was assessed by the presence of ciliated cells, goblet (mucin-producing) cells, and basal epithelial cells. Scanning electron microscopic observations revealed both ciliated and non-ciliated cells in these 3D tissues. Histological examination revealed the presence of mucin-producing cells, and immunohistochemistry using antibodies against p63 and keratin 14 showed the presence of basal cells. These results demonstrate that immortalized HBECs retain the capacity to differentiate into each of three cell types: basal, mucin-producing, and columnar ciliated epithelial cells. Such cells will be useful cellular reagents for research in aging, cancer progression, as well as normal bronchial epithelial differentiation and will help progress the use of engineered cells to enhance tissue regeneration.
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PMID:A three-dimensional model of differentiation of immortalized human bronchial epithelial cells. 1668 84


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