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

The effect of purified extracellular matrix components (EMC) as mediators of cell attachment was studied in vitro using two related murine mammary adenocarcinomas with different metastasizing ability. Freshly harvested cells from M3, the less metastatic tumor, exhibited a similar low affinity for fibronectin, laminin, type IV collagen and the control protein albumin, while the highly metastatic MM3 cells attached preferentially to fibronectin. On the other hand an enhancement of the spreading and adhesion rate to the EMC was observed after primary culture. MM3 cultured cells showed almost the same affinity for all EMC while M3 cells specially attached to fibronectin and type I collagen. The data indicate that in vitro passage can modify the adhesion behavior of these metastatic adenocarcinoma cells to EMC.
Invasion Metastasis 1986
PMID:Modified adhesion behavior after in vitro passage of two related murine mammary adenocarcinomas with different metastasizing ability. 378 87

A series of rasH oncogene-transformed cell lines were established from NIH-3T3 cells using the calcium phosphate precipitation method of transfection. The transfectant lines formed highly-invasive tumors when injected into athymic mice while the parent cells did not. When examined for motility in the micropore filter assay, all of the transfectant lines were motile in response to either laminin or fibronectin while the parent cells were not stimulated by either factor. These studies, therefore, indicate that transformation of NIH-3T3 cells with the rasH oncogene results in the generation of cells with increased capacity for motility relative to the parent cells.
Invasion Metastasis 1986
PMID:Motility of rasH oncogene transformed NIH-3T3 cells. 380 40

Metastasizing tumor cells must traverse diverse extracellular matrices during dissemination. Extracellular matrices consist of two basic types, interstitial stroma and basement membranes. Extracellular matrices are chemically complex structures that interact with cell surfaces by a number of mechanisms. There has been a great deal of effort in recent years to understand the molecular nature of extracellular matrices, especially as it relates to the adhesion of normal and malignant cell types. Adhesive noncollagenous glycoproteins, such as laminin and fibronectin, serve pivotal roles in basement membrane and stromal matrices, respectively. These proteins participate in establishing the architecture of extracellular matrices as well as in attaching to the surface of cells and affecting cellular phenotype. This phenotypic effect ranges from adhesion and motility to growth and differentiation. Changes in adhesive characteristics and motility of cells have long been suspected to play a role in mediating the spread of malignant neoplasms. This article is designed to review extracellular matrix constituents that are currently known that can mediate the adhesion and motility of malignant neoplasms. The adhesion of normal and malignant cells to matrices is a complex process mediated by several distinct mechanisms which are initially manifested by changes in cytoskeletal architecture. The topic of normal and malignant cell adhesion to matrices will also be discussed in this regard, since any explanation of tumor cell migration must account for the complex dynamic interactions of the cell surface with the substratum as well as with the cytoskeleton. Finally, current efforts designed to understand the molecular nature of tumor cell:matrix interactions that contribute to metastatic behavior will also be discussed. The rationale behind these studies is that selective inhibition of specific tumor:extracellular matrix interactions can provide an avenue for therapeutic intervention of metastatic cancer.
Cancer Metastasis Rev 1985
PMID:The role of cell adhesion proteins--laminin and fibronectin--in the movement of malignant and metastatic cells. 389 83

This study examined gel filtered rat platelet activation by Walker 256 rat carcinoma cells and characterized fibronectin release. Using aggregometry measurements, a biphasic platelet response was characterized and the timing of alpha granule release was determined. The localization and association of released platelet fibronectin with tumor cell-platelet aggregates was determined by immunofluorescent and immunocytochemical methods. The immunofluorescent studies showed that the platelet fibronectin was released and became associated with the peripheries of the tumor cells following alpha granule discharge. The ultrastructural immunocytochemical data revealed that this fibronectin was associated with a fibrin-like material, enmeshing the tumor cell-platelet aggregates. The significance of the release and localization of platelet fibronectin to tumor cell metastasis is discussed.
Clin Exp Metastasis
PMID:Platelet fibronectin release induced by Walker 256 rat carcinoma tumor cells. 390 1

The loss of fibronectin from tumor cell surfaces has been correlated with an increased incidence of metastases. To determine directly whether cell surface fibronectin influences the metastatic potential of solid tumors, we chemically crosslinked fibronectin to B16 murine melanoma cells using a photosensitive heterobifunctional crosslinking reagent, N-succinimidyl-4-azidophenyl-1,3 dithiopropionate (SADP). Cell attachment to plastic surfaces was increased in cells to which fibronectin was attached; cell growth over a 24-hr period was not significantly affected by the addition of fibronectin. When C57BL/6 mice were injected with fibronectin-crosslinked B16 cells, there was a 63% reduction in the number of pulmonary nodules compared to untreated controls. These results are consistent with the hypothesis that fibronectin enhances the recognition and removal of tumor cells from the circulation, possibly by cells of the reticuloendothelial system.
 ...
PMID:Altered characteristics of B16 melanoma cells induced by chemically crosslinking fibronectin to cell surfaces. 399 Mar 5

By implantation of BSp73 ascites cells in a subcutaneous site and subsequent subcutaneous passage of either the local tumor node or metastatic lung tissue, variants were obtained which differed with respect to morphology and to metastatic capacity. The highly metastasizing variant ASML showed spherical morphology in culture, while the nonmetastatic variant AS showed adhesion and spreading. Upon cloning it was observed that colonies with fully expressed morphotypes were readily obtained from solid tissue of both variants. Parental ascites as well as the tumor line derived from the primary solid tumor gave rise to stable expression of either morphotype only after prolonged culturing. Mixing of established clones did not result in an interclonal adaptation of growth rates in vivo. Further characterization of variants AS and ASML revealed marked differences in the outer cell surface. Adhesion of AS cells onto plastic was found to be mediated by fibronectin, laminin and 4 out of 5 collagen types. ASML cells showed adhesion only with collagen type III at higher concentrations. Cytogenetic analysis revealed that the adaptation of BSp73 cells to ascitic growth ultimately led to an increase in chromosome numbers, and this was conserved in ASML cells (modal number 63, range 49-74). AS cells on the other hand showed a modal number of 47 (range 45-49). The chromosome count distribution was rather narrow in ascites cells in vivo, but it was very broad in clones derived thereof, indicating that diversity was obtained in culture rather than in vivo. The data are compatible with the assumption that the nonmetastatic variant was not preexisting in BSp73 ascites but represents a stable phenotype which infrequently arises in a particular microenvironment by chromosome loss from a hyperdiploid parental population.
Invasion Metastasis 1985
PMID:Clonal analysis of diversity in the BSp73 rat tumor. 406 7

In this review, evidence that proteoglycans are involved in cell adhesion and related behavior is considered, together with their putative role(s) during tumorigenesis. Proteoglycans are large, carboxylated and/or sulfated structures that interact with specific binding sites on cell surfaces. Their distribution and synthesis in tissues alter with the onset of tumorigenesis so that hyaluronic acid is generally increased and heparan sulfate decreased in the developing tumor and surrounding tissue. However, the precise role of proteoglycans during the tumorigenic process is far from clarified. Data suggest any putative roles will be related to the adhesive properties that these molecules confer to cells. Hyaluronic acid and chondroitin sulfate appear to be weakly adhesive molecules that may promote 'transformed' characteristics when they occur on cells in large amounts. These characteristics include reduced cell spreading, increased cell motility, as well as reduced contact inhibition. Consistent with such properties, neither hyaluronic acid nor chondroitin sulfate are localized in specialized adhesion sites such as focal or close contacts. In contrast, heparan sulfate is associated with increased cell-substratum adhesion and is involved in the spreading of cells onto fibronectin and other substrata. Its presence is generally associated with reduced motility and with a well-spread morphology. Unlike hyaluronate and chondroitin sulfate, heparan sulfate is found in specialized contacts. These adhesive properties of proteoglycans predict an instructive role in tumor development, and recent experiments have defined an involvement of these molecules in metastatic arrest. Additional studies utilizing invasive and metastatic tumor variants including tumor cells that employ different mechanisms to invade are required to clarify the role of proteoglycans in tumor progression.
Cancer Metastasis Rev 1984
PMID:Proteoglycans and cell adhesion. Their putative role during tumorigenesis. 608 29

Cysteine proteinases are a subclass of endopeptidases which require activation by thiol reagents. A tumor cysteine proteinase which appears to be related to lysosomal cathepsin B has been implicated in the ability of tumor cells to invade the extracellular matrix and to metastasize to secondary sites. Lysosomal cathepsin B can degrade such components of the extracellular matrix as collagen, fibronectin and proteoglycans. Activity of this cathepsin B-like cysteine proteinase (CB) has been correlated with tumor malignancy in a number of tumor lines yet not in all tumor lines studied. CB activity in tumors seems to be associated with the viable tumor cells, probably with the plasma membrane of these tumor cells. CB activity has been measured in the sera, urine, ascites fluid and pancreatic fluid of tumor-bearing patients. CB is released from tumor explants and tumor cells in vitro as well as from normal subcutaneous tissue exposed to tumor-conditioned medium. Cathepsin B from normal tissues is rapidly inactivated above pH 7.0. Therefore, CB in tumor cell membranes or released from tumor cells (or from host cells in response to tumor cells) may not possess proteolytic activity at neutral pH and thus may not facilitate tumor cell invasion. However, CB exhibits enhanced stability at neutral or slightly alkaline pH's. There is not yet definitive proof that CB plays a role in tumor invasion and metastasis. There is, however, an increasing body of correlative evidence relating CB activity and tumor malignancy. This correlative evidence plus preliminary evidence that tumor CB can degrade components of the extracellular matrix in vitro suggests that CB may be one proteinase active in a proteolytic cascade resulting in tumor invasion and metastasis.
Cancer Metastasis Rev 1984
PMID:Cysteine proteinases and metastasis. 609 95

The distribution of actin, myosin, fibronectin and basement membrane antigens has been studied by indirect immunofluorescence in benign and malignant human breast lesions. While benign tumors showed only minor differences from normal mammary tissue, tumors of different histological types displayed a heterogeneous distribution of the antigens studied. Heterogeneity was observed within the same tumor, among different neoplasms and between primary tumors and autologous metastases. As a common characteristic, most of the tumors did not stain for actin and myosin, the pattern being similar to that found in myoepithelial cell distribution. In transformed epithelia there was often a lack of detectable actin with a myosin-positive fluorescence. Staining for both proteins was diffused to most of the cell cytoplasm. Staining for fibronectin was seen in only a minority of the cases, with medullary tumors being the most positive. Basement membrane stain was either absent or decreased and fragmented, except in rare ductal, i.e. papillary, carcinomas. Medullary tumors displayed an almost continuous, though fragmented basement membrane in approximately 70% of cases.
 ...
PMID:Heterogeneous distribution of actin, myosin, fibronectin and basement membrane antigens in primary and metastatic human breast cancer. 609 24

An association between cancer and the coagulation system was suggested by Trousseau more than a century ago and initial reports of fibrin deposition in the stroma of solid tumors date back some 25 years. However, the validity and generality of these observations have only quite recently been established, and their implications for an understanding of tumor biology, metastasis, and therapy are only now coming to be appreciated by investigators in the mainstream of cancer research. This article reviews the current status of fibrin's role in the biology of tumor growth, considering in turn: (1) the evidence that fibrin is present in tumors, the nature of such fibrin, and its relation to plasma fibronectin; (2) the mechanisms by which fibrin may come to be deposited in tumors; and (3) the potential biological and medical significance of tumor-associated fibrin deposition and degradation. Among the last are such important possibilities as a barrier function to the immune response and possible roles in angiogenesis, desmoplasia, and metastasis.
Cancer Metastasis Rev 1983
PMID:Fibrin as a component of the tumor stroma: origins and biological significance. 619 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>