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)

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.
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PMID:Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells. 288 31

From the highly metastatic in vivo-passaged Friend leukemia cells (FLC), WGA-resistant (WR) tumor cell variants were selected. These WR FLC had lost their capacity to metastasize when injected i.v. or s.c. into DBA/2 mice. We have characterized the plasma membrane glycoproteins of the different FLC types by: (i) metabolic labelling with (3H)-galactose; (ii) surface labelling with galactose oxidase-borohydride; (iii) direct binding of (125I)-lectins on glycoproteins separated by SDS-PAGE. The ensemble of these approaches showed that the 100- to 200-kDa glycoproteins of in vivo-passaged FLC and WR FLC exhibited a very similar distribution of the terminal galactose in their oligosaccharide moieties. In contrast, the expression of terminal sialic acid was reduced in WR FLC with respect to in vivo-passaged counterparts as appreciated by: (i) binding experiments with (125I)-WGA; (ii) cathodic shift of the 100- to 200-kDa glycoproteins in 2-dimensional electrophoresis studies, and (iii) thiobarbituric acid assay after FLC treatment with neuraminidase. Moreover, binding experiments with (125I)-LPHA, (125I)-ConA and (125I)-WGA (after Smith degradation) indicated that, in the 100- to 200-kDa region, virtually identical asparagine-linked tri- or tetra-antennary complex-type oligosaccharides were expressed in both cell types. We conclude that the sialylation of high-molecular-weight surface glycoproteins (particularly in the 150-kDa region) is strongly associated with the metastatic potential of FLC, especially to the liver.
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PMID:Hyposialylation of high-molecular-weight membrane glycoproteins parallels the loss of metastatic potential in wheat-germ agglutinin-resistant Friend leukemia cells. 291 Aug 24

Expression of plasminogen activator (PA) activity may be an important factor in the ability of tumour cells to metastasize; however, not all metastatic cells produce detectable PA activity. Conditioned culture media from revertant metastatic clones of cells derived by fusion of metastatic and non-metastatic rat mammary adenocarcinoma cells were found to contain a potent inhibitor of PA. This inhibited thrombin, human urokinase (UK) and tumour-derived PA, but not plasmin or trypsin. Inhibition was still obtained after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE) of mixtures of PA and inhibitor, followed by development of PA activity on fibrin overlays. The PA inhibitor eluted from Sephadex G-200 over a broad M.wt. range (35,000-80,000) and was inactivated by heating to 70 degrees for 30 min. The appearance of inhibitory activity in the culture media was time-dependent and could be reduced by incubation of cells with cycloheximide. Because of these findings, the possible presence of inhibitors should be considered in investigations into the role of PA in the metastatic process.
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PMID:An inhibitor of plasminogen activator produced by tumour cell fusion hybrids. 293 23

We have used binding of radioactive lectins (i.e. Concanavalin A (ConA), Wheat Germ Agglutinin (WGA) and Ricinus communis agglutinin I (RCAI)) to membrane glycoproteins separated in SDS gel electrophoresis, to detect specific carbohydrate changes in plasma membrane proteins of in vivo passaged Friend erythroleukemia cells (FLC). These cells are highly metastatic to the liver, whereas the original in vitro passaged tumor cells do not metastasize. Marked qualitative differences in the high molecular weight region of the gels (100-200 kD) were observed between the WGA binding glycoproteins of metastatic in vivo passaged FLC and nonmetastatic in vitro passaged FLC. Furthermore, the binding of WGA to plasma membrane proteins of in vivo passaged FLC was much greater than the binding of WGA to plasma membrane proteins of in vitro passaged FLC. Lectin binding experiments after sialic acid removal by in situ mild acid hydrolysis of FLC glycoproteins indicated that an increased sialylation of the 120 and 145 kD glycoproteins was responsible for the increased WGA reactivity of in vivo passaged FLC plasma membranes. Besides the increased sialylation, other changes in glycosylation of the 100-200 kD glycoproteins of in vivo passaged FLC were observed: (1) qualitative differences between the WGA binding patterns of the two cell types were restored after treatment of the gels with mild acid and subsequent Smith degradation; (2) after chemical removal of sialic acid residues from the gels, qualitative differences in the RCA binding patterns to the glycoproteins of the two cell types were apparent.
Clin Exp Metastasis
PMID:Wheat germ agglutinin-binding protein changes in highly malignant Friend leukemia cells metastasizing to the liver. 316 57

Lectin-binding characteristics of a previously described highly metastatic variant (clone 4), derived in vivo from a poorly metastatic rat mammary adenocarcinoma (DMBA-8), have been investigated. of the lectins studied clone 4 cells, unlike the parent cells, bound Ulex europaeus agglutinin (UEA-1; specificity alpha-L-fucose) and peanut agglutinin (PNA; specificity D-galactose). These differences may be related to the greatly enhanced ability of clone 4 cells to form lung foci after intravenous injection. After neuraminidase treatment the differential binding of PNA, as shown by flow cytofluorography, was abrogated whereas that of UEA was unchanged. After separation by SDS-PAGE, four proteins in total cell extracts of clone 4 cells bound 125I-UEA applied to the gels. These had subunit molecular weights greater than 100,000 daltons and were also found in cellular extracts of another highly metastatic rat mammary adenocarcinoma (MAT 13762-B), but were missing from DMBA-8 cell extracts. In clone 4 and MAT 13762-B cells exogenous 3H-fucose was mainly incorporated into four fucoproteins of similar molecular weights to those which bound 125I-UEA. DMBA-8 cells, which incorporated slightly less exogenous fucose, showed a different pattern of fucoprotein labelling, which would seem to explain why DMBA-8 cells failed to bind UEA. Differences in cell surface protein iodination patterns were also noted between DMBA-8 and clone 4 cells.
Invasion Metastasis 1987
PMID:Lectin-binding characteristics of related high- and low-metastatic rat mammary adenocarcinoma cell lines. 367 43

Highly metastatic cell lines have been isolated from lung foci formed by the intravenous injection of large numbers (5 X 10(6)) of cells of a poorly metastatic rat mammary adenocarcinoma (DMBA-8). The metastatic variant lines were phenotypically different and, unlike the parent line, produced high levels of plasminogen activator (PA) separable into three major bands (MW 30,000, 48,000 and 83,000) on SDS-PAGE. It is suggested that PA may play a role in the enhanced metastatic ability of these cells. Using parallel DMBA-8 clones the rate of generation of the metastatic variant cells was estimated, by fluctuation analysis, to be approximately 1.85 X 10(-6) per cell generation.
Invasion Metastasis 1986
PMID:Enhanced plasminogen activator production by highly metastatic variant cell lines of a rat mammary adenocarcinoma. 373 65

Isolation of a melanoma-specific protein (MSP) from human urine has been achieved using antibody affinity chromatography. MSP migrates as a single homogeneous protein on SDS PAGE and comparison of these data and ultracentrifuge analyses indicates that MSP contains a single polypeptide chain. MSP, however, shows considerable charge heterogeneity on isoelectric focusing. The desialo form, alpha 2 MSP, is found predominantly in patients with advanced metastatic disease, whilst only the sialo form alpha 1 MSP, is obtained from the urine of patients with early-stage disease. MSP does not react with antisera raised to alpha 1 foetoprotein (AFP) or carcinoembryonic antigen (CEA) and hence is immunologically distinct from these other tumour-associated glycoproteins. Antisera raised to MSP do not react with normal skin melanocytes nor with any foetal tissue tested, and hence the origin of MSP remains unresolved.
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PMID:Further characterization of a melanoma-specific protein from human urine. 615 65

In order to investigate the possible correlation between plasminogen activator (PA) activity and metastatic potential of tumour cells, we studied cultured cells from the murine fibrosarcoma mFS6 and from its two sublines M4 and M9 which differ markedly in their capacity to cause spontaneous metastases in the lung. PA activity was detected in all the sublines by an amidolytic method and was almost completely inhibited by treatment with antiurokinase antiserum. No significant differences were shown between mFS6, M4 and M9. Moreover, molecular analysis of PA by SDS-PAGE electrophoresis and fibrin overlay revealed in all the cell types a single species having a mol. wt. of approximately 48,000 daltons. Thrombin treatment dramatically inhibited the amidolytic activity of all cells, suggesting a role for this enzyme in the modulation of fibrin formation and dissolution within the primary neoplasm.
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PMID:Plasminogen activator activity of metastatic variants from a murine fibrosarcoma; effect of thrombin in vitro. 668 49

We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small dimensions, the same technique was not applicable to vesicles. For these structures dot-blot analysis and immunoelectron microscopy (IEM) were employed. When applicable, both cell membranes and membrane vesicles were immunoprecipitated and the precipitate (IP) was analyzed by SDS-PAGE. Cells of both lines expressed HLA class I antigens, epithelial cytokeratins, beta 1 integrins, CEA and the glycoprotein detected by mAb 19.9, but only MCF-7 cells expressed Lewis Y, episialin and globo-H antigens and only 8701-BC cells expressed folate receptor. Membrane vesicles of both cell lines appeared to be rich in beta 1, alpha 3 and alpha 5 integrin chains, expressed HLA class I antigens and carried most of the plasma membrane antigens found in the cell membranes. Overall we have analyzed 17 antigens on the two cell lines and on their vesicles. The results obtained for cells (IF and IP) and those for vesicles (dot-blot and IP) were generally concordantly positive or concordantly negative. We obtained a total of 26 clearly concordant combinations on 34 analyses. In three cases we found discordant results, whereas in the remaining combinations we observed slight reactivity and we found difficulties in determining concordance. Discordant results concerned the expression of the following antigens: folate receptors, which were clearly expressed in 8701-BC cells but not detected by dot-blot analysis or IEM on their shed membrane vesicles; neu (c-erb-B2) receptor found in MCF-7 cell membranes but not in their vesicles; and the globo-H antigen recognized by mAb MBr1, detected at low levels on 8701-BC plasma membranes but undetectable on their membrane vesicles. Like vesicles shed in vitro by cultured cells, the vesicles shed in vivo by human breast carcinoma cells could be tagged with several antibodies against tumor-associated antigens. The vesicles shed in vivo were found in association with a fiber network. Some of the fibers had the characteristic fibrin periodicity. These data suggest that tumor markers detected in the circulation of carcinoma patients, at least in part, are carried by shed membrane vesicles. Moreover the observation that membrane vesicles carry both tumor-associated antigens and HLA class I molecules indicate that these structures could in principle present antigens to the immune system.(ABSTRACT TRUNCATED AT 400 WORDS)
Clin Exp Metastasis 1995 Jul
PMID:Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens. 760 90

A M(r) 78,000 protein (reduced), termed invasion stimulating factor (ISF), was purified from the conditioned medium of a bone metastasizing human prostatic PC-3 ML clone (M. E. Stearns and M. Stearns. Cancer Metastasis Rev., 12: 39-52, 1993). Scatchard analysis and affinity cross-linking studies revealed that the producer PC-3 ML cells expressed a receptor binding site (M(r) approximately 115,000). We found a Kd approximately 425 pM and about 22,000 sites/cell. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiograms confirmed that the PC-3 ML cells expressed the receptor, whereas the ISF non-producing, noninvasive PC-3 clones (i.e., 3-4 x N.I. PC-3 cells) failed to express the ISF receptor. We conclude that a unique ISF autocrine loop characterizes the bone metastatic PC-3 ML cells.
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PMID:Identification of the receptor for a novel M(r) 78,000 "invasion stimulating factor" from metastatic human prostatic PC-3 ML clones. 816 99


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