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)

We examined the effect of medroxyprogesterone acetate (MPA) on secondary spreading of endometrial cancer. There was no significant difference in the adhering capacity of dispersed Ishikawa cells (derived from well-differentiated endometrial cancer) to a cell basement membrane matrix, fibronectin or laminin between cells treated with MPA, with cortisol, and without treatment. The adhering capacity of cells treated with cortisol to collagen type IV was higher than that without treatment. However, the adhering capacity was little affected by treatment with MPA. These results indicate that although cortisol may induce the initial process of metastasis by inducing the attachment of tumor cells to the basement membrane of vascular endothelium, MPA has no influence on the attachment, although it has a glucocorticoid action similar to that of cortisol. There was no significant difference in tumor angiogenesis factor (TAF) or fibroblast growth factor (FGF) activity of the tumor extract from Ishikawa cell colonies between cortisol-treated and control group. TAF or FGF activity of the MPA-treated group was lower than that of the control group. MPA may reduce the neovascularization in the terminal process of metastasis via the reduction of TAF and FGF produced by tumor cells, in spite of its glucocorticoid action.
Invasion Metastasis 1989
PMID:Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer. 252 39

Cell fusion experiments have predicted the existence of cancer metastasis suppressor genes. The E1a gene of Adenovirus 2 has been demonstrated to suppress c-Ha-ras induction of experimental metastatic potential in rat embryo fibroblasts. Another approach to the identification of candidate metastasis suppressor genes has utilized differential or subtraction hybridizations to clone genes which are downregulated as cells become highly metastatic. To date, three such genes have been identified: nm23, WDNM1, and fibronectin. With regard to nm23, downregulation of nm23 RNA levels in high metastatic potential cells has been demonstrated in a wide variety of rodent metastasis systems, including K-1735 murine melanoma cell lines, nitrosomethylurea-induced rat mammary tumors, MMTV-induced mouse mammary tumors, and ras +/- E1a transfected rat embryo fibroblasts. Whether the expression of the nm23 gene, and other down-regulated genes in tumor metastasis, correlates with changes in metastatic potential, or actually has suppressive activity, will require transfection experiments.
Invasion Metastasis 1989
PMID:Search for metastasis suppressor genes. 253 85

A new, sensitive automated assay based on the enzyme-linked immunosorbent assay was developed for measuring proteolytic enzyme activity produced by metastatic tumor cells. In this assay, a suitable protein substrate is adsorbed onto the surface of microplates and incubated with dilutions of standard proteinases, viable tumor cells, or tumor-cell-conditioned medium. The loss of immobilized protein due to proteolysis is then detected by means of antibodies directed against the target protein, and is measured by a microplate reader. Both casein and fibronectin were useful as substrates for the assay of various well-defined proteinases. The assay was successfully used to detect degradative activity elaborated by the mouse B16-BL6 melanoma and the human HT1080 fibrosarcoma cell lines. Both cell lines extensively removed immobilized protein substrates when the cells were seeded directly on the protein films. In addition, substrate removal could also be detected in the serum-free culture medium conditioned by the tumor cells. The results indicate that soluble proteinases secreted by tumor cells may be important during tissue invasion.
Invasion Metastasis 1989
PMID:Solubilization of immobilized protein substrates by metastatic tumor cells. 264 47

In order to study the effect of estrogens and antiestrogens on the adhesive properties of human breast cancer cells, the attachment on endothelial cells (EC), on subendothelial extracellular matrix (ECM) and on ECM components (collagen I and IV, laminin, fibronectin) of estrogen-dependent (MCF-7, ZR75-1) and estrogen-independent (BT-20) breast cancer cell lines was investigated. The cells were grown under conditions of controlled exposure to estrogen [17 beta-estradiol (E2)] and/or antiestrogens [tamoxifen (Tam) or 4-hydroxytamoxifen (OH-Tam)]. Treatment by E2 enhanced the ability of ZR75-1 cells to adhere to the various substrates, which contrasts with the observed absence of effects with the BT-20 cells. Similarly, Tam or OH-Tam induced a reduction of the adhesion of ZR75-1 tumor cell, but not of BT-20 cells. This effect was reversed by competing concentrations of E2. The effects on MCF-7 cell adhesion were similar to those described for ZR75-1 cells, but could not be reproducibly observed. Adhesion assays carried out with ZR75-1 cells grown in the absence or presence of phenol red, a pH indicator which behaves as a weak estrogen, led to a similar pattern of cell attachment. Conditioned media harvested from E2- or Tam-treated ZR75-1 cells failed to induce any effect on adhesion of other ZR75-1 cells grown in E2-deprived medium, suggesting that secretory activities are not required for the control of cell adhesiveness. The results suggest that estrogens and antiestrogens can control the adhesive behavior of breast tumor cells through their hormone responsive structures possibly by regulating expression of cell adhesion proteins and/or their cell surface receptors.
Clin Exp Metastasis
PMID:Modulation of human breast cancer cell adhesion by estrogens and antiestrogens. 270 28

The adhesive, invasive, and growth properties of parental murine large-cell lymphoma cells of low metastatic potential (RAW117-P) were compared to in-vivo-selected sublines of high metastatic potential to liver (RAW117-H10) or lung (RAW117-L17). Using small (approximately 0.5 mm3) pieces of syngeneic organ tissue (lung, liver, kidney) we found that RAW117-L17 cells selectively attached to and invaded lung tissue, whereas RAW117-H10 cells preferentially attached to and invaded liver tissue. We measured adhesion to microvessel endothelial cells established from syngeneic lung and liver and found that the RAW117-L17 cells bound to lung microvessel endothelial cells at significantly higher rates than the other lines, and RAW117-H10 and -L17 cells attached to hepatic sinusoidal endothelial cells at significantly faster rates than RAW117-P cells. Such organ specificity of adhesion was not found at the level of the subendothelial matrix, and the rates of adhesion of RAW117 cells to subendothelial matrix were lower than to endothelial cells. RAW117 cells of low or high metastatic potential bound to immobilized extracellular matrix components, such as fibronectin, at high rats, but adhesion to laminin or collagen IV was minimal. Previous studies indicated that RAW117 lines could proliferate in vitro in certain organ-conditioned media under limiting serum conditions. We therefore examined the ability of a purified paracrine lung growth factor (LDGF-1) to stimulate growth of RAW117 cells in limiting serum-containing medium. The high lung-colonizing L17 line was stimulated to proliferate by LDGF-1 at faster rates than the other lines. The data support Paget's hypothesis that the organ specificity of tumor metastasis is determined by specific tumor cell and host properties.
Invasion Metastasis 1989
PMID:Adhesive, invasive, and growth properties of selected metastatic variants of a murine large-cell lymphoma. 270 4

A synthetic peptide derived from the B1 chain of laminin, F-9, as well as two peptides derived from the 33-kilodalton fragment of fibronectin, I and II, directly promoted the adhesion of K-1735-M4 metastatic murine melanoma cells. In competition assays, adhesion of these cells to laminin was inhibited by excess soluble peptide F-9. Peptides F-9, I, and II specifically bound 3H-heparin, both by direct binding assays and indirect competition assays. 3H-heparin binding to peptide F-9 was specific as determined by competition with excess unlabeled heparin, dextran sulfate, and dermatan sulfate. These findings suggest that melanoma cell surface associated heparin-like molecules may act as receptors for these domains of laminin and fibronectin.
Invasion Metastasis 1989
PMID:Novel synthetic heparin binding peptides of laminin and fibronectin which promote the adhesion of melanoma cells. 270 7

The interaction of malignant cells with blood-vessel endothelial cells and their underlying basement membrane is an important step in the development of secondary metastases. We investigated the interactions of highly metastatic human tumor cells, the A-549 adenocarcinoma of the lung, with cultured endothelial cells (EC) and their extracellular matrix (ECM). We studied the adhesion patterns of the A-549 tumor cells to EC and ECM under static and flow conditions. Our results provide evidence that tumor-cell adhesion depends not only on the characteristics of the tumor cells themselves, but also on the properties of the EC and ECM. Our results also indicate that tumor-cell adhesion to ECM is shear-rate-dependent, and that it is partially modulated by fibronectin. Moreover, our results suggest that the arg-gly-asp (RGD) common adhesion receptor site is also involved in the adhesion of the A-549 cells to EC and ECM.
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PMID:Influence of shear stress on tumor-cell adhesion to endothelial-cell extracellular matrix and its modulation by fibronectin. 273 6

Cell ultrastructure, extracellular matrix glycoproteins, and type IV collagenolytic activity have been examined in four murine TS/A clones characterized by different metastatic aggressiveness. In vitro, highly metastatic clones (E) exhibited slightly less differentiated ultrastructure, and high type IV collagenolytic activity, while low metastatic clones (F) showed a more differentiated cytotype, with either high and low collagenolytic activity. Type IV collagen, laminin, and fibronectin were expressed without correlation with the metastatic efficiency; keratin was slightly more evident in E than in F cells. The morphological differences between E and F clones were less evident in the tumors produced by subcutaneous injection, and markedly reduced in the relative metastases composed only of the less differentiated cytotype; differences were also reduced in cells cultured on extracellular-matrix-coated flasks. The present study shows that no general correlation is observed between the studied parameters and metastatic aggressiveness.
Invasion Metastasis 1988
PMID:Different metastatic aggressiveness by murine TS/A clones: ultrastructure, extracellular glycoproteins and type IV collagenolytic activity. 283 29

In this report we describe the isolation and characterization of a neutral metalloproteinase, from human small cell lung cancer cells, which degrades a wide range of connective tissue proteins. Treatment of tumor cytosol by ammonium sulphate precipitation followed by zinc chelated column chromatography, anion exchange chromatography, and gel filtration chromatography yielded a single enzymatically active protein, which on SDS-PAGE appeared as a diffuse band of 65,000-70,000 daltons. The tumor metalloproteinase, which was inhibited by metal chelators and serum, was able to digest gelatin, type I collagen, type IV collagen, laminin, and fibronectin. We propose that the capacity of this proteinase to degrade both components of blood vessel basement membranes and other connective tissue matrices facilitates the dissemination of human lung cancer cells during the multistep process of metastasis.
Clin Exp Metastasis
PMID:Characterization of a connective tissue degrading metalloproteinase from human small cell lung cancer cells. 283 54

The ascitic fluid concentrations of cholesterol and fibronectin and the serum-ascites albumin difference were compared with two conventional tests of ascitic fluid, total protein and LDH, in their diagnostic ability for detection of malignancy in ascitic samples from 69 patients with ascites: 54 with ascites due to liver disease and 15 whose ascites was caused by peritoneal metastases. Sixteen cirrhotic patients with superimposed hepatocellular carcinoma in whom ascites was of uncertain etiology were considered separately. The mean ascitic fluid total protein, LDH, cholesterol, and fibronectin values in the peritoneal metastases group were 3.70 +/- 1.20 g/dl, 247.26 +/- 148.14 units/liter, 109.06 +/- 29.85 mg/dl, and 91.57 +/- 41.52 micrograms/ml, respectively, and all were significantly higher than the corresponding values in the liver disease group (P less than 0.001), which were 1.37 +/- 0.59 g/dl, 75.40 +/- 110.70 units/liter, 23.75 +/- 11.22 mg/dl, and 31.86 +/- 10.51 micrograms/ml, respectively. Mean serum-ascites albumin difference in the peritoneal metastases group was 0.62 +/- 0.38 g/dl, which was significantly different from the corresponding value in the liver disease group (1.92 +/- 0.41 g/dl, P less than 0.001). Both ascitic cholesterol above 46 mg/dl and an ascitic fibronectin concentration greater than 50 micrograms/ml had high diagnostic accuracy (97%) for malignancy, being higher than that achieved using a serum-ascites albumin difference under 1.1 g/dl and an ascitic total protein above 2.5 g/dl, which had accuracies of 94% and 93%, respectively. Ascitic fluid LDH was the least reliable test. No differences in the ascitic fluid analysis were found between cirrhotic patients with and without hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnosis of malignant ascites. Comparison of ascitic fibronectin, cholesterol, and serum-ascites albumin difference. 283 70


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