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)

The effects of human recombinant interleukin-1 alpha and beta (rIL-1 alpha; rIL-1 beta) on the adhesion of human A549 lung carcinoma cells and M6 melanoma cells (TC) to human endothelial cells (HECs) in vitro were studied, and on TC/lung entrapment in vivo. In vitro, there was a significant increase in TC/HEC adhesion to HECs pretreated for 4 h with rIL-1 alpha or rIL-1 beta. The effects of rIL-1 alpha and beta on TC/HEC adhesion were time dependent and reached a plateau within 4-6 h. TC/HEC adhesion was not blocked when measured in the presence of antibodies to either fibronectin, glycoprotein IIb/IIIa, anti-ICAM, or anti-LFA. However, enhanced TC/HEC adhesion was completely blocked in the presence of the peptide, GRGDS. In vivo, pretreatment of nude mice for 4 h with rIL-1 alpha (given i.p. before i.v. injection of TCs) enhanced TC retention in the lung 24 h later. Our data demonstrate that IL-1 enhances TC adhesion to the vascular surface both in vitro and in vivo, suggesting that IL-1 can facilitate the metastatic process.
Clin Exp Metastasis
PMID:Interleukin-1 increases tumor cell adhesion to endothelial cells through an RGD dependent mechanism: in vitro and in vivo studies. 229 11

A panel of tumor cell lines and clones was generated by selecting for different metastatic capacity in 3AM fibrosarcoma cells. These cell lines were exposed to substrata of various purified extracellular matrix (ECM) proteins and labeled in culture with [35S]methionine. Following analysis by two-dimensional polyacrylamide gel electrophoresis the profiles of total cellular proteins produced by the cell lines displaying different phenotypes were examined. The presence of a specific protein, p54, was related to the cellular metastatic potential, and the synthesis of p54 was influenced by growth on extracellular matrix components. The amount of p54 was minimal and non-inducible in tumor cell lines exhibiting two different phenotypes: (1) experimentally metastatic (EM) and (2) transformed, non-tumorigenic (NTT) cell types. In contrast, all of the five different cell lines capable of both spontaneous and experimental metastasis (SEM), produced p54 either constitutively or through induction by growth on ECM protein substrata of either laminin of fibronectin, but not collagen type IV. These data suggest that the p54 protein may be a unique biochemical marker associated with spontaneous metastatic cell types.
Clin Exp Metastasis
PMID:Expression of a specific protein in spontaneously metastatic fibrosarcoma cell lines and its enhanced synthesis by growth on laminin or fibronectin. 229 13

Using the Matrigel invasion assay, we have examined the role of cell adhesion and migration in the invasiveness of two cell lines, DM and HSR, derived from the Y1 mouse adrenocortical tumor. The DM cells were metastatic and more invasive (10-fold) than the nonmetastatic HSR cells. The difference in invasiveness could not be ascribed to different levels of secreted type IV collagenolytic activity since HSR cells secreted higher levels of activity. Cells from the metastatic DM line showed greater motility to both laminin and fibronectin when compared to the HSR line. Furthermore, both Matrigel and laminin promoted the attachment and spreading of DM cells but they had little effect on the adhesion of the HSR cells. Electron microscopic examination revealed an increased ruffling of the cell membrane in the metastatic DM line. These studies suggest a role for cell adhesion and migration on the invasion of Matrigel by malignant tumor cells.
Invasion Metastasis 1990
PMID:The role of cell adhesion and migration in the in vitro invasiveness of mouse adrenal carcinoma cells. 235 27

Experiments were performed to determine the relative effects of glycosaminoglycans and extracellular matrix components alone or in association with various substrates, including extracellular matrix, on the proliferation of rat rhabdomyosarcoma (RMS) cell lines of different metastatic potential and nontumorigenic rat myoblast L6 cells. The assays used various substrates: tissue culture plastic, type I and IV collagen, fibronectin, laminin and extracellular matrix deposited by corneal endothelial cells. In control experiments, tumor cells grew faster on fibronectin and extracellular matrix than on the other substrates, and their proliferation rate was decreased slightly by laminin. Collagens were growth-inhibitory only for the highly metastatic line. The proliferation rate of L6 myoblasts was not greatly affected by the different substrates. The addition of exogenous glycosaminoglycans to the culture medium modified cell proliferation on the various substrates. Heparin inhibited the growth of all the cell lines tested, independent of the substrate. When cultured on laminin substrate the proliferation rates of the cell lines were depressed by addition of heparan sulfate to the medium, and this effect was more pronounced in the metastatic RMS lines. Chondroitin sulfate and dermatan sulfate enhanced the growth rates of the tumorigenic cells when cultured on collagen type I surfaces. Hydrocortisone, which induces myogenic differentiation, decreased the cell proliferation rates of all the cell lines tested and intensified the inhibitory effects of heparin when added simultaneously to the culture medium. The results showed that glycosaminoglycans and other matrix components can affect the proliferation rates of rhabdomyosarcoma cell lines.
Clin Exp Metastasis
PMID:Effects of glycosaminoglycans and extracellular matrix components on metastatic rat rhabdomyosarcoma tumor and myoblast cell proliferation. 239 Aug 14

Angiogenesis is indispensable to sustain promotion and growth of metastases. As a contribution to the understanding of the angiogenesis process, the experiments reported showed that: (a) fibronectin is involved in the mobilization of capillary endothelium which is the first event in angiogenesis; (b) antifibronectin serum can block the mobilization, and neutralization of the antiserum can restore it; (c) the combination of fibronectin + heparin is a powerful mobilizer of capillary endothelium, and (d) fragments of the fibronectin and heparin molecules in combination can mobilize capillary endothelium as effectively as the intact molecules. The results are interpreted to indicate that molecules normally present in the extracellular matrix like heparin and fibronectin, may act as angiogenesis effectors when the physiological structure of the tissue is altered, for instance by lytic enzymes released by metastatic neoplastic cells.
Invasion Metastasis 1985
PMID:Cooperation between fibronectin and heparin in the mobilization of capillary endothelium. 240 44

Tumor angiogenesis is a very important process for growth and proliferation of most solid tumors. It insures the delivery of feeding molecules as well as the elimination of degradation products and allows tumoral cells to escape from the primary tumor site and the further establishment of metastases. Tumor neovascularisation is the result of a cascade of events primarily related to the properties of endothelial cells of capillaries. The main steps are: a) degradation of capillary basal lamina and destruction of the surrounding tissues, b) endothelial cell proliferation and c) endothelial cell migration towards the tumor site. A number of substances either synthetic or of natural origin are known to stimulate one of the above mentioned steps and/or to induce the production of factors which, in turn, stimulate one or several steps of the cascade. Such molecules can also be synthesized by tumoral cells; indeed they have often been evidenced in the fluids surrounding the tumor site. Many factors remain to be identified and their mechanism of action wait to be elucidated. However, it is already clear that several molecules are involved in the various steps of tumor angiogenesis. They display a coordinated sequential action and their synthesis is induced and controlled by the tumor itself. Amongst others, the following molecules play a role in tumor angiogenesis: degradative enzymes, E-prostaglandins, specific oligopeptides, fibronectin and heparin. Furthermore, several metal cations are also involved in tumor angiogenesis.
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PMID:[Tumor angiogenesis]. 242 24

Mobilization of the capillary endothelium is one of the first events observed during angiogenesis, and the study of conditions that control or influence the mobilization of the endothelium in vitro has been assumed to offer information relevant to the understanding of angiogenesis in vivo. In vitro mobilization of the bovine capillary endothelium was substantially enhanced by addition of gangliosides to the culture medium. Optimal mobilization was obtained when the endothelium incorporated the gangliosides first and was then seeded on fibronectin anchored to collagen type I. Preincubation of the capillary endothelium with gangliosides, trisialoganglioside in particular, doubled the amount of fibronectin bound to the cells and enhanced the migration about 5-fold. 'Blockage' of ganglioside binding with cholera toxin or gamma-interferon substantially reduced migration. Rabbit corneas, treated in vivo with a variety of angiogenesis effectors to induce neovascularization, consistently showed an increase in sialic acid content just prior to the time the tissue would be penetrated by the capillaries. This finding was interpreted to indicate that an increment of the ganglioside content of the capillary endothelial cell membranes may play a determinant role in the mobilization of the capillary endothelium in vivo as shown here to take place in vitro. Since the formation of a tumor from a micrometastasis requires formation of new capillaries and highly metastasizing tumors very frequently have high levels of sialic acid on the cell surface, it is hypothesized that production and shedding of gangliosides from the surface of neoplastic cells may be a factor in promoting angiogenesis and metastatic growth.
Invasion Metastasis 1986
PMID:Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastasis. 242 14

The functional properties of the melanoma-associated antigens detected by monoclonal antibodies (MAbs) AMF-6 and AMF-7 were investigated. These MAbs were selected previously because of their capacity to block the anti-melanoma reactivity of cytotoxic T-lymphocyte clones AMF-6 and AMF-7 detect a melanoma-associated proteoglycan (MW greater than 450-250 kDa) and a molecular complex, which under reducing conditions consists of 4 compounds of 120, 95, 29 and 25 kDa respectively. AMF-6 reacted strongly with all 30 cultured melanomas and all 41 melanomas in frozen tissue sections. Significant cross-reactivity was only observed with nevi and perineurium, whereas normal skin melanocytes were negative. AMF-7 reacted with all 25 cultured melanomas and all 34 melanomas in frozen sections. AMF-7 cross-reacted with a proportion of nevi and endothelial cells from small vessels. The antigen detected by AMF-6 and AMF-7 could not be modulated by retinoic acid or recombinant gamma-IFN, which induced or enhanced the expression of HLA-DR, HLA-DQ and Class-I MHC antigens. In addition, the antigens were not readily modulated when cells were incubated in excess amounts of AMF-6 and AMF-7. Interestingly, the antigen detected by AMF-7 was strongly associated with the adhesion and cytoplasmic spreading of melanoma cells to plastic surfaces and monolayers of vascular endothelial cells. AMF-6 did not block the adhesion of melanoma cells but delayed cytoplasmic spreading. Both AMF-6 and AMF-7 blocked fibronectin-induced chemotaxic motility and chemokinesis of melanoma cells. In addition to their membrane localization, the antigens detected by AMF-6 and AMF-7 were also abundant in extracellular adhesion plaques deposited by cultured melanoma cells. Our results indicate that the high-MW melanoma-associated proteoglycan and the antigen detected by AMF-7 are associated with adhesion and/or cytoplasmic spreading and motility of human melanoma cells, suggesting that these antigens are associated with the (hematogenic) dissemination of human melanoma. This is supported by the finding that AMF-7 stained primary tumors heterogeneously, whereas metastases were homogeneously stained.
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PMID:Characterization of melanoma-associated surface antigens involved in the adhesion and motility of human melanoma cells. 242 58

The peripheral stromal fibronectin (FN) staining patterns of invasive breast carcinomas (IBC) from 77 women were compared to the aggressivity of the tumors, which in each case had been determined through a complete clinical follow-up and autopsy investigation. Polyclonal, monospecific rabbit antibody to human FN was applied on formalin-fixed, paraffin-embedded tissue sections using the peroxidase-antiperoxidase staining technique. An FN-positive staining reaction was defined as a constant, diffuse, or pericellular demarcation of FN-positive fibers surrounding tumor cells at the invasive border. In lack of such a staining pattern, FN-negative staining was recorded. The FN-positive staining reaction was significantly associated with a low metastatic potential and appeared in a multivarians analysis to be an excellent prognostic factor, which surpassed other known parameters, such as clinical stage, histological type or grade, and lymph node status. 27 out of 31 women, who died without evidence of metastatic spread, had FN-positive IBC (87%) in contrast to women with metastatic disease, where only 15 out of 46 had FN-positive tumors (33%). An extensive histopathological examination of the contralateral breast revealed in this latter group a high rate of second primaries (22/46), which might have been responsible for the metastatic spread. If these women with bilateral IBC were excluded, only three metastasizing tumors with a FN-positive staining pattern remained, suggesting that the prognostic value of the FN-staining pattern along the invasive border of IBC might be even higher than anticipated from this study.
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PMID:Stromal fibronectin staining pattern and metastasizing ability of human breast carcinoma. 245 33

Hyaline globular inclusions were found in a case of malignant melanoma. The globules were both intracellular and extracellular in the primary neoplasm and in metastases to lymph nodes, liver, and lung. They were studied immunohistochemically and were found to contain fibronectin, a glycoprotein of high molecular weight. Ultrastructurally, the globules were composed of electron-dense, finely fibrillar aggregates. It is suggested that the neoplastic cells produced the fibronectin, which accumulated in globular form. Ten additional cases of malignant melanoma were studied; none of these had hyaline globules or intracellular globular fibronectin. The globules were compared to similar structures described in Spitz's nevi and other neoplasms. Immunohistochemical analysis was most useful in distinguishing the globules found in the malignant melanoma from those found in other conditions.
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PMID:Fibronectin-containing hyaline globules in malignant melanoma. 248 47


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