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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has examined cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies did not reveal any consistent differences in glycoprotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which cannot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation.
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PMID:Effects of altering surface glycoprotein composition on metastatic colonisation potential of murine mammary tumour cells. 310 27

Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.
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PMID:Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. 311 96

Platelet-adhesive protein-tumor cell interaction was studied in vitro and in vivo. Monoclonal antibody 10E5, which inhibits binding of fibronectin and von Willebrand factor to the platelet membrane glycoprotein GPIIb-GPIIIa complex, inhibited the binding of mouse CT26 and human HCT8 colon carcinoma cells to platelets by 63-65%, whereas an irrelevant monoclonal antibody, 3B2, had no effect. Monoclonal antibody 6D1, which inhibits binding of von Willebrand factor to GPIb, also had no effect. RGDS, a tetrapeptide that represents the adhesive domain of fibronectin and von Willebrand factor inhibited binding of the tumors to platelets by 64-69%. Monospecific polyclonal antifibronectin antibody inhibited binding by 60-82%; anti-von Willebrand factor antibody inhibited binding by 75-81%. In vivo, polyclonal monospecific anti-mouse von Willebrand factor antibody inhibited pulmonary metastases induced by CT26 tumor cells by 53-64%, B16a amelanotic melanoma cells by 45% and T241 Lewis bladder cells by 46% without induction of thrombocytopenia. Pulmonary metastases with CT26 cells could be inhibited by induction of thrombocytopenia, and reconstituted by infusion of either murine or human platelets. Reconstitution of pulmonary metastases with human platelets could be inhibited 77% by preincubation of human platelets with monoclonal antibody 10E5 before infusion of platelets into mice. Thus, platelets appear to contribute to metastases by their adhesive interaction with tumor cells via the adhesive proteins fibronectin and von Willebrand factor.
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PMID:Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. 328 May 98

Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the MeWo human malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other lectins, membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial" metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these metastases were deeply pigmented facilitating visual identification of very small visceral metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine tumor MDAY-D2 which are known to be deficient in sialic acid and galactose. The similarity between these and earlier results using lectin resistant mutant rodent cell lines strongly suggests that sialylated glycoconjugates contribute to the metastasis of both animal and human tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human tumor progression in vivo and factors involved in metastasis, especially the contribution of oligosaccharide moieties of cell surface glycoconjugates.
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PMID:Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. 333 29

The distribution of laminin, a basement membrane glycoprotein, was studied by indirect immunofluorescence technique using rabbit anti-laminin serum in fifty-seven samples of normal, hyperplastic, adenomatous and carcinomatous colorectal tissue. As judged by the expression of laminin normal, hyperplastic and adenomatous colorectal mucosa were characterized by a continuous, linear basement membrane. A thick band-like basement membrane was seen under the surface epithelium and at the mouths of the crypts in normal and hyperplastic mucosa. The adenomatous epithelium was uniformly characterized by a thin, linear basement membrane. In contrast, marked alterations were constantly observed in colorectal carcinomas and their metastases, which showed a discontinuous, linear or patchy basement membrane. Our study suggests that the expression of laminin is related to cellular differentiation, and the thickness of the laminin-positive basement membrane parallels with the epithelial maturation of normal and hyperplastic colorectal mucosa and with the failure of the epithelial differentiation in adenomas. In colorectal carcinomas and their metastases the distribution of laminin is constantly altered and the severity of the alterations correlates with the histological grade of these tumours.
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PMID:Malignant transformation in human colorectal mucosa as monitored by distribution of laminin, a basement membrane glycoprotein. 405 Apr 37

Human and murine tumor cells contain cell surface receptors for the basement membrane glycoprotein laminin. Since a biologic role for the receptor had not previously been demonstrated, we explored the possibility that the laminin receptor may be involved in hematogenous metastases formation. Preincubation of metastatic murine melanoma cells with syngeneic whole laminin followed by tail vein injection increased tumor cell retention in the lung and strongly stimulated metastases formation. The domain of the laminin molecule responsible for stimulating metastases was identified. Laminin is a cross-shaped molecule with three short arms and one long arm. All arms have globular end regions. Purified protease-derived fragments of laminin were prepared which (a) lacked only the long arm of the molecule (alpha fragment) or, (b) lacked both the long arm and the globular end regions of the short arms (C1 fragment). Both types of fragments contained the laminin receptor binding region. The fragments had opposite effects on metastases. The alpha fragment stimulated metastases formation to the same extent as whole laminin. In contrast, the C1 fragment greatly reduced or abolished metastases formation in a dose-dependent manner. The C1 fragment also inhibited tumor cell attachment to whole amnion basement membrane in vitro. We conclude that intact globular end regions on the short arms (but not the long arm) of the cell surface receptor-bound laminin molecule are necessary for stimulating metastases by the intravenous route.
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PMID:Laminin molecular domains which alter metastasis in a murine model. 608 86

The distribution of the basement membrane glycoprotein laminin was studied by the immunoperoxidase technique in benign and malignant human breast tissue and in axillary lymph nodes from patients with breast cancer. An antiserum prepared against rat laminin was used. The specificity of this antiserum against human laminin was studied using the FL cell line of human epithelial-like cells derived from normal amniotic membrane. The antiserum reacted with these cells in immunoperoxidase staining and precipitated metabolically labeled secreted polypeptides which comigrated with polypeptides with molecular weights of 400,000 and 200,000 of rat laminin in sodium dodecyl sulfate:polyacrylamide gel electrophoresis. The neoplastic cells in malignant breast tissues showed strong cytoplasmic staining for laminin, and a positive reaction was aslo found in lymph node metastases. In some cases in which only micrometastases were present, these cells also stained strongly for laminin. In nonmalignant breast tissues, the epithelial cells of the duct were positive for laminin, but the staining was weaker than in the carcinomas. Pretreatment of the fixed tissue sections with trypsin markedly enhanced the staining of basement membranes for laminin. In trypsin-treated sections of normal breast tissue and benign lesions, the laminin staining delineated continuous basement membranes. In carcinomas representing the more differentiated types, basement membranes presumably produced by the tumor cells could be revealed by laminin staining, but they were thinner and discontinuous. The poorly differentiated carcinomas lacked organized basement membranes detectable by laminin staining. Our studies suggest that staining for laminin may be a useful adjunct test for detection of micrometatases in lymph nodes. The correlation of disintegration of the laminin-containing basement membranes of tumors with increasingly anaplastic appearance supports the notion that basement membranes may play a role in tumor invasion.
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PMID:Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin. 703 Apr 83

The lecture reviews some aspects of the work on the analysis of malignancy that have been, and are now being, pursured in the Dunn School. A brief outline of the early experiments that first demonstrated that the malignancy of mouse tumor cells can be suppressed by the fusion with normal cells is given, and then two areas of current interest in the laboratory are described. The first is an attempt to analyze the clinically important property of tumors to metastasize and the second is the work on the isolation and identification of an abnormal membrane glycoprotein present in tumor cells. In addition the value of cell fusion methods as a general test of hypotheses of malignancy is emphasized.
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PMID:The analysis of malignancy by cell fusion. 718 79

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. The expression of CD44 in 23 gastric adenocarcinoma and 12 peptic ulcer disease (PUD) resection specimens and gastric carcinoma cell lines HS746t and KATO III was examined by immunohistochemistry using the murine monoclonal antibody A3D8 on formalin-fixed, paraffin-embedded tissue or cells. Western blot analysis of whole cell lysates of KATO III and HS746t cells showed protein bands at 85 to 90 kd with KATO III cells expressing an additional band at 145 kd. In normal stomach gastric epithelium was negative. In PUD foveolar epithelium was focally positive, but staining did not correlate with the extent of gastritis. In carcinoma cases intensity of staining was progressively stronger comparing intestinal metaplasia with dysplasia with intramucosal carcinoma. Invasive carcinoma was invariably more strongly positive than dysplasia or intramucosal carcinoma. Twelve adenocarcinomas were weakly positive and 11 were strongly positive. The staining intensity of metastases (12 cases) was the same or weaker than the primary tumor. For the 12 patients whose carcinomas were weakly positive, mean length of survival for the six who died was 23.3 months. Five of the 11 patients whose carcinomas strongly expressed CD44 died within the study period with a mean length of survival of 11.0 months. A key consequence of CD44 overexpression in gastric carcinomas may be development of the invasive phenotype and strong expression may indicate a poorer prognosis.
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PMID:Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas. 752 75

We report a case of a primary renal primitive neuroectodermal tumour in a 24-year-old man associated with multiple pulmonary metastases. Histologically, the bulk of the kidney was replaced by a small round-cell tumour with numerous true Homer-Wright rosettes and perivascular pseudorosettes; wide-spread vascular invasion was noted. There was no evidence at autopsy of a primary tumour elsewhere. Immunohistochemically, the tumour cells stained strongly positive for O-13, a monoclonal antibody, which recognizes a recently described cell membrane glycoprotein (p30/32MIC2), more weakly for NSE and at least focally for PGP 9.5; the tumour did not stain for other neural markers, cytokeratin, leucocyte common antigen, or desmin. The differential diagnosis of small round-cell tumours in this location and the relation of primitive neuroectodermal tumours and Ewing's sarcoma are discussed.
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PMID:[Primary primitive neuroectodermal tumor of the kidney in an adult. Clinico-pathologic and immunohistochemical case report]. 797


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