Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of fibronectin (FN) isoforms containing the extradomains A and B (ED-A+ and ED-B+ FNs) as well as a differentially O-glycosylated oncofetal form of the protein (onf-FN) was investigated in 6 normal human anterior pituitaries and 25 human pituitary adenomas. In normal tissue, immunohistochemical experiments showed the presence of FN molecules lacking the extradomains A and B (ED-A- and ED-B- FNs) without onf-FN immunoreactivity. These proteins were localized in the connective tissue compartment and especially in the vessel walls. Analysis of FN mRNA demonstrated an in situ synthesis of ED-A- and ED-B- FNs in the normal anterior pituitary. By contrast, in the adenomas, immunoreactivity for ED-A+ FN was observed in all cases. ED-B+ and onf-FN immunoreactivities were observed in 14 and 8 adenomas, respectively, regardless of the type, grade or invasiveness of the adenomas. ED-A+ FN mRNA was expressed in all adenomas studied, and ED-B+ FN mRNA was present in ED-B+ immunoreactive cases only. In pituitary adenomas, these 3 forms of FN were specifically associated with the endothelium and vascular smooth-muscle cells. Our results demonstrate that the processes of remodelling of the connective tissue compartment that occur in adenoma angiogenesis are associated with pre- and post-translational alterations of FN synthesis leading to the expression of ED-A+, ED-B+ and oncofetal FNs.
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PMID:Fibronectin isoforms are differentially expressed in normal and adenomatous human anterior pituitaries. 770 30

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.
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PMID:Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. 800 99

The distribution of fibronectin in the normal and pleomorphic adenoma of the salivary gland was investigated in forty cases of surgically resected tumor specimens. The immunoreactivity of fibronectin using polyclonal antibody (anti-fibronectin A2 45, Dakopatts, Denmark) was detected in the cytoplasm of intercalated duct cells and certain striated duct cells in normal salivary glands. Pleomorphic adenoma showed few fibronectin positive cells with a scattered or isolated distribution within the epithelial tumor elements of tubulo-ductal or solid foci of tumor cells. Modified myoepithelial cells and luminal cells of tubulo-ductal structures reacted strongly to fibronectin. In hyalinous, myxoid and chondroid areas, fibrillary myoepithelial cells expressed strongly positive reactivity but with diffuse staining in the myxoid and chondroid areas suggesting that fibronectin plays an important role in tumor cell-extracellular matrix interactions to produce the complex histopathological features of pleomorphic adenoma.
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PMID:Fibronectin expression in salivary gland pleomorphic adenoma. 823 49

Phenotypic characteristics of cells and extracellular matrix (ECM) of 14 salivary gland pleomorphic adenomas were studied by indirect immunofluorescence. All cells in the epithelial structures expressed cytokeratin 8, the majority of cells produced vimentin, laminin and IV type collagen. Cells of myxoid areas expressed vimentin: type IV collagen was observed in the form of fibrillar structures. Fibrous areas were characterized by vimentin and cytokeratin 8 expression; types I, III, IV collagens and fibronectin with ED-A sequence were present in ECM. Terms "epithelial structures", "epithelial" and "myoepithelial" cells in relation to pleomorphic adenoma may be used only relatively as it is mainly represented by cells with features of both epithelial and mesenchymal phenotype. Characteristics of ECM synthesized in various structures of pleomorphic adenoma may serve an additional criterion of cell transformation.
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PMID:[Phenotypic characterization of cells and structure of the extracellular matrix in pleomorphic adenoma of the salivary glands]. 933 57

Changes in integrin expression during malignant transformation have been observed in many tumors. Colon-carcinoma cells show reduced expression or even loss of the alpha5beta1 integrin compared to normal or adenoma cells. To determine the significance of absent alpha5beta1 integrin signaling, we transfected the cDNA coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line HT29, which constitutively lacks this subunit but does express the beta1 subunit. We show here that the newly expressed fibronectin receptor alpha5beta1 generates multiple signals, causing marked changes in cytoskeletal arrangements within a few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin exhibit the formation of actin stress fibers and focal adhesions, as well as the induction of tyrosine phosphorylation of several proteins, within 10 min. We identified the focal adhesion kinase pp125FAK and the cytoskeletal protein paxillin as major phosphorylation substrates in these cells. These proteins remained hypophosphorylated when alpha5-negative control cells were plated on fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation of cellular proliferation and constitutively over-expressed in HT29 and in colon-carcinoma cells, showed reduced intrinsic kinase activity in unstimulated HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1 increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor during malignant transformation may contribute to tumor-cell autonomy, while reduced activity of pp60c-src in HT29alpha5-cells may participate directly in growth control.
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PMID:De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on fibronectin. 953 67

A morphological study of biopsy samples of gastric polyps from 224 patients was carried out. Four stages in gastric polyp morphogenesis were distinguished: foveolar hyperplasia, hyperplastic polyp, "two-floor" adenoma and adenoma. The correlation was established between the degree of Helicobacter pylori infection in the polyp mucous membrane on the one hand, and epithelial and stromal reactions (immuno-inflammatory reaction of stroma, chronic inflammation, formation of Russel bodies, cystes and chronic erosions) on the other. Greater content of stromal collagens, type IV collagen in case of gastric hyperplastic lesions was observed. Appearance and progression of gastric adenomatous growth in hyperplastic polyp correlates with an increase of type III collagen content, decrease of types I, IV, V collagens and fibronectin.
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PMID:[Morphological characteristics of hyperplastic and adenomatous stomach polyps]. 961 4

The aim of the study was to confirm earlier reports of the association of amyloid deposits in growth hormone (GH)-producing adenomas of the pituitary and the presence of glycosaminoglycans, basement membrane proteins and apolipoprotein E (apo E). Serial sections from 17 amyloidotic and 11 nonamyloidotic, sparsely granulated, GH-producing adenomas obtained from patients presenting with acromegaly were stained with Congo red and Alcian blue, and also with antisera directed against fibronectin, collagen IV, laminin and apo E. Glycosaminoglycans were found in capillaries of every adenoma and were also related spatially to amyloid deposits. Immunostaining of both nonamyloidotic and amyloidotic adenomas demonstrated the presence of fibronectin, collagen IV and laminin in the basement membranes of surrounding nonadenomatous tissue and tumour vessels. In approximately half the amyloidotic adenomas, each basement membrane protein presented with a distinct spatial relationship to amyloid deposits. Apo E was found in 88% of the amyloidotic adenomas within the amyloid deposits, and in six cases intracellular immunostaining was also evident in folliculo-stellate cells. The results are consistent with the presence of glycosaminoglycans, basement membrane proteins and apo E in the amyloid deposits of pituitary adenomas.
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PMID:Basement membrane proteins, apolipoprotein E and glycosaminoglycans in pituitary adenomas and their correlation to amyloid. 969 22

The extracellular matrix (ECM) conveys signals through membrane receptors called integrins producing changes in cell morphology, proliferation, differentiation and apoptosis. Previous studies suggest that the ECM plays an important role in pituitary physiology and tumorigenesis. In the present work we studied for the first time the effects of fibronectin, laminin, collagen I and collagen IV on hormone secretion and cell proliferation in the corticotroph tumor cell line AtT-20 and in normal pituitary cells, examining the signal transduction mechanisms that mediate these effects. ACTH production in AtT-20 cells was inhibited by fibronectin, laminin and collagen I. A reporter construct with the POMC promoter showed similar results, indicating that the effects of the ECM take place at the level of POMC gene transcription. In contrast, ACTH production was not significantly altered in normal pituitary cells. AtT-20 cell proliferation was stimulated by collagen IV and fibronectin, but inhibited by collagen I and laminin. In parallel, the cell morphology was modified by the ECM. We found that the production of reactive oxygen species mediate the effects of laminin and collagen IV. On the other hand, the effect of fibronectin was mimicked by beta1-integrin and Rho activation. These results show for the first time that the ECM controls ACTH biosynthesis and proliferation in corticotroph tumor cells and suggest a role for the ECM in corticotroph adenoma development.
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PMID:Extracellular matrix components regulate ACTH production and proliferation in corticotroph tumor cells. 1132 24

Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on alpha v beta 6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both alpha v beta 6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK). Furthermore, phosphorylated ERK was targeted to newly forming cell--matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK--tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK--ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK--ERK--dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression.
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PMID:The protrusive phase and full development of integrin-dependent adhesions in colon epithelial cells require FAK- and ERK-mediated actin spike formation: deregulation in cancer cells. 1149 15

The role of pericytes (PCs) during embryonic or tumor angiogenesis is a matter of debate. We studied the expression of cytoskeletal, membrane, and matrix markers in experimental tumors of the human mammary ductal adenoma MDA-MB231 cell line that were grown on avian chorioallantoic membranes (CAMs) from incubation day 10 to 18 (chick) or 8 to 15 (quail). The expression patterns of alpha-smooth muscle actin (alphaSMA) and desmin, of adhesion molecules beta1 integrin and neurothelin, and of fibronectin and laminin were analyzed with conventional and confocal laser scanning microscopy. The CAM arterial wall showed strong alphaSMA signal in all smooth muscle cell layers but the innermost layer, which was desmin positive. Ramified alphaSMA-negative cells with delicate desmin staining accompanied most minor vessels and were also seen basal to the capillary plexus indicating the presence of PCs. In the tumor nodules, a diffuse alphaSMA signal without definite relationship to vascular structures was detected. Strongly desmin-positive, alphaSMA-negative cells were frequent in the zone of contact to the CAM in small nodules, and were scattered in larger tumors. In some regions they were associated with microvessels, and in others appeared detaching from endothelial cells (ECs) or as single migrating cells. We conclude that: (a) the CAM tumor angiogenesis assay is useful for studying PC/EC interactions, (b) PCs are recruited from the CAM into experimental tumor nodules, (c) variability of vasculature in MDA-MB231 tumors may be due to variable PC/EC interactions, and (d) alphaSMA should be used with caution as a general PC marker.
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PMID:Pericytes in experimental MDA-MB231 tumor angiogenesis. 1210 3


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