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

Weakly (RMS8) and highly (RMS0) metastatic rat rhabdomyosarcoma cells were assayed for their interaction with hyaluronate. The cells in subconfluent cultures were incubated with 35S methionine, the cells were fractionated and the labelled proteins were separated by affinity chromatography on hyaluronate-Sepharose and by HPLC. The RMS8 cells expressed about twice the amount of labelled hyaluronate-binding proteins seen in the RMS0 cells. The molecular sizes of the main hyaluronate-binding proteins were similar in both cell types. Unlike the RMS0 cells, the RMS8 cells took up exogenous, radioactively labelled hyaluronate at 4 degrees C in a saturable and specific way with high affinity. Cells were also incubated with 3H glucosamine. The isolation of the glycosaminoglycans from these cultures by ion-exchange chromatography indicated that the RMS8 cells retained more endogenous 3H hyaluronate in their pericellular domain than did the RMS0 cells. The attachment of trypsinized cells could be inhibited with exogenous hyaluronate, indicating that the proteins with affinity for hyaluronate may act as hyaluronate-binding sites on these cells.
Clin Exp Metastasis
PMID:Hyaluronate-binding proteins in weakly and highly metastatic variants of rat rhabdomyosarcoma cells. 169 Jun 19

The Glycosylation inhibitors, glucosamine or tunicamycin induced a marked loss of pigment within melanoma cells in addition to their reduced metastatic ability. Electrophoresis of tyrosinase demonstrated the disappearance of or a marked decrease in membrane-bound tyrosinase, T3 in the small and large-granule fractions. Glycoprotein synthesis in the melanogenic subcellular compartments of pigment cells seems to play an integral role in melanogenesis which is principally enhanced in their carcinogenic status. The effect of interferon (IFN) on melanoma metastasis was investigated using B16-F10 melanoma cells. The inhibitory effect was maximal when given 3 h prior to tumor cell inoculation. IFN given 12 and 24 h prior to, as well as simultaneously with, tumor cell inoculation, also reduced metastases, but to a lesser extent. When given 2 h after the inoculation, no effect was shown. The salutary effect of IFN was abolished by anti-asialo GMI, but NK activity was enhanced equally throughout 3 to 24 hrs. This indicates that the effect is substantially dependent on NK cell activity, although the implication of other factors is not excluded.
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PMID:[Control of melanogenesis by glycosylation inhibitors and the inhibitory effect of interferon on melanoma metastasis]. 240 78

Invasion of malignant MO4 cells into embryonic chick heart fragments in an organ culture assay was arrested for at least 7 days when the temperature was lowered to 28 degrees C. Prolonged culturing of MO4 cells at 28 degrees C on tissue culture substrates showed no recuperation of fucose incorporation into cell surface glycopeptides. However, invasion was restored after 10 days of organ culture in confrontation with chick heart tissue at 28 degrees C. A histoautoradiographic study showed that the regained capability to invade was accompanied by an increase in fucose labeling of the MO4 cells in the invading areas. At 28 degrees C the incorporation of [3H]fucose into total cell protein was drastically reduced, whereas [3H]leucine incorporation as a measure for protein synthesis was less affected. Cell surface glycopeptides, metabolically labeled with either fucose or glucosamine at 28 degrees C, showed a time-dependent decrease in the incorporation of fucose but not of glucosamine and no changes in overall size distribution. Low temperature did not reduce fucosyltransferase activity but the relative accumulation of fucose-1-P suggested inhibited conversion towards GDP-fucose. Moreover, mouse L cells which were incapable of invading chick heart tissue appeared also deficient in fucose incorporation, owing to low levels of fucosyltransferase activity. According to the results, fucosylation of surface carbohydrates may be required for invasive capacity and restored in MO4 cells invading at 28 degrees C by metabolic cooperation with the host tissue.
Clin Exp Metastasis
PMID:Decreased fucose incorporation in cell surface carbohydrates is associated with inhibition of invasion. 275 7

The glycosaminoglycans (GAGs) of low (LM) and highly metastatic (HM) cell lines of the Lewis lung tumour (3LL) were compared using [3H]glucosamine labelling techniques. The GAGs isolated from nuclei, cytoplasm, pericellular fractions and medium were analysed by cellulose acetate electrophoresis and by digestion with specific enzymes, and the following conclusions were drawn. 1. Increased cellular uptake and incorporation of [3H]glucosamine into glycoconjugates of the cytoplasm was a typical feature of the highly metastatic cell line after a 48-h labelling. However, there was no elevated radioactivity in glycolipids. 2. Radioactivity of the purified GAGs was two and three times higher in nuclear and cytoplasmic fractions of HM cells than in those of LM cells. There was much less difference between the two cell lines in the pericellular fractions. 3. A definite change from chondroitin sulphate to dermatan sulphate dominancy was recorded in each GAG fraction. Higher heparan sulphate labelling was observed in the cytoplasmic and pericellular GAGs of HM cultures. 4. In the post-labelling period about three times more GAG was present in the extracellular compartment of the HM cultures compared with the LM cultures. 5. In the LM cultures the total GAG-associated radioactivity decreased by 73 per cent in the 48-h chase period whereas in the HM cultures it decreased by only 30 per cent. This indicates a higher rate of GAG degradation in the LM cultures.
Clin Exp Metastasis
PMID:Comparative study on Lewis lung tumour lines with 'low' and 'high' metastatic capacity. III. Glycosaminoglycan synthesis, transport and degradation in cell lines. 277 70

Penetration of the extracellular matrix (ECM) by tumor cells, an event which occurs at various stages of the metastatic process, involves tumor cell glycosidase mediated hydrolysis of proteoglycans (PG). Recently, we observed that human ovarian carcinoma cell lines (HOCC) derived from primary tumors, peritoneal effusions, and distant metastases possess a varying ability to degrade radiolabeled PG of the ECM, while normal cells (human mesothelial cells or ovarian fibroblasts) fail to do so. To determine whether a quantitative relationship exists between glycosidase activity and degradation of ECM, both intracellular and extracellular glycosidase activities were measured for HOCC and normal cell lines. No relationship was found between intracellular glycosidase activities and the ability of cells to degrade ECM. However, a correlation was observed between extracellular or secretory glycosidase activities and HOCC mediated ECM degradation. In particular, a 5-8-fold increase, as compared to normal cells, was observed for HOCC extracellular beta-N-acetylglucosaminidase (EC 3.2.2.30) activity. The accumulation or secretion of this enzyme from HOCC into culture medium was found to be time dependent and not related to intracellular levels. Purified hexosaminidase derived from invasive HOCC was able to hydrolyze [3H]-glucosamine radiolabeled ECM (up to 30% radiolabel) and resulted in the cumulative release of free [3H]-N-acetylglucosamine. This enzyme mediated hydrolysis could be completely prevented with 2-acetamido-2-deoxy-1,5-D-gluconolactone, a competitive inhibitor (Ki 10(-6) M). Finally, HOCC mediated degradation of radiolabeled ECM was discerned to be dependent upon active hexosaminidase action, since tumor cell mediated degradation of ECM could be inhibited by up to 60% in the presence of this synthetic competitive inhibitor. In summary, these studies indicate a strong association between HOCC solubilization of glycoconjugates present in the ECM and extracellular levels of hexosaminidase.
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PMID:Role of glycosidases in human ovarian carcinoma cell mediated degradation of subendothelial extracellular matrix. 295 46

The enhanced metastatic capacity of an in vivo selected Lewis lung tumor line (LLT-HH) was correlated with changes in cell-associated glycosaminoglycans (GAG) using ultrastructural cytochemistry, flow cytometry and biochemistry. The increase in highly sulphated GAG content on the cell membrane of LLT-HH cells compared to the parent LLT cells was demonstrated cytochemically. Using in vitro [3H]glucosamine labelling of GAG components it was shown that the LLT-HH cells were characterized by a high production of heparan sulphate while the parent LLT line had a high hyaluronic acid-chondroitin sulphate production. The high metastatic phenotype is accompanied by an altered production of cell-associated GAGs.
Clin Exp Metastasis
PMID:Comparative study on Lewis lung tumor lines with 'low' and 'high' metastatic capacity. II. Cytochemical and biochemical evidence for differences in glycosaminoglycans. 310 61

Better in vitro models are needed to elucidate the mechanisms underlying tissue destruction by human tumor cells. To address this matter recently isolated and characterized human ovarian carcinoma cell lines derived from either primary tumors, ascitic effusions or metastatic growths were plated in direct contact with extracellular matrix (ECM) previously deposited on culture dishes by bovine corneal endothelial cells. Light and electron microscopy of four of the five ovarian tumor cell lines demonstrated morphologic digestion with penetration of ECM by tumor cell microvilli, along with associated rarefaction. The ability of these same ovarian tumor cell lines to solubilize specific carbohydrate and protein moieties present in intact ECM was assessed with the use of metabolically prelabeled ECM employing tritiated fucose, galactose, glucosamine and proline. Results from these studies corroborated morphologic observations in which four of the five tumor cell lines tested extensively solubilized radiolabeled ECM. The kinetics of radiolabel release from ECM illustrated that three of the four invasive tumors released [3H]fucose, [3H]glucosamine and [3H]proline at high rates. Normal human ovarian fibroblasts and mesothelial cells were observed to be unable to digest ECM and this was consistent with their inability to release radiolabeled material from prelabeled ECM. The results from these studies suggest that some ovarian carcinomas have the ability to degrade basement membrane components. Knowledge regarding the mechanisms responsible for tissue degradation may eventually lead to the development of new chemotherapeutic modalities designed to restrict tumor cell invasion, growth and metastasis.
Clin Exp Metastasis
PMID:In vitro degradation of extracellular matrix by human ovarian carcinoma cells. 329 49

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials, grown in the presence or in the absence of hydrocortisone and of growth factor (EDF and EDGF) were investigated comparatively. The newly formed [35S]sulphate and [3H]glucosamine-labelled glycosaminoglycans were analysed in the extra-, peri- and intra-cellular compartments of the following cell lines: the strongly metastatic and colonizing 9-4/0 parental line, the very weakly metastatic and weakly colonizing subline 8 and the very weakly metastatic but colonizing subline 13a2. The cell surface of the weakly metastatic 8 and 13a2 lines was richer at least 5 and 2 times respectively in sulphated glycosaminoglycan label than the surface of the strongly metastatic 9-4/0 parental line. Hydrocortisone provoked an approximately four-fold increase in the label of the sulphated cell surface glycosaminoglycans of the 9-4/0 line. The pattern of the labelled cell surface glycosaminoglycans of these cells become similar to that of cells from the very weakly invading subline 8. Hydrocortisone induced only minor changes in the distribution of the glycosaminoglycans in the 8 and 13a2 lines, and at the same time, their proliferation rate and differentiation state was only slightly affected by this drug. Conversely to hydrocortisone, EGF increases the proliferation of the 9-4/0 line and also increases the label in sulphated cell surface glycosaminoglycans. This increase is about 50 per cent of that obtained by hydrocortisone. Thus, the accumulation of the glycosaminoglycan label on the cell surface is not directly related to the cell growth in the case of these cells. The results suggest that sulphated cell surface glycosaminoglycans, especially chondroitin sulphate, are involved in the inhibition of metastasis formation of the rhabdomyosarcoma cell lines studied.
Clin Exp Metastasis
PMID:Modulation of proteoglycan metabolism by hydrocortisone and by growth factors in rhabdomyosarcoma cell lines of different metastatic potentials. 387 51

Variant subpopulations of FM3A mouse mammary carcinoma cells increasing lung-colonizing potential were obtained by previously sequentially harvesting pulmonary metastases, culturing their cells in vitro, and reestablishing the metastases in vivo. In the present study, glycosaminoglycan production by the parental and variant cells was studied after metabolic labeling of cultures by [14C]glucosamine for 24 hr. Analysis of the products indicated that the rate of incorporation of the labeled precursor into hyaluronic acid in the high-metastatic variant cells was 27 to 54 times the rate in the low-metastatic cells and that the increase in hyaluronic acid synthesis was not associated with an increase in the rate of synthesis of other glycosaminoglycans. Both the cell layers and media of high-metastatic variants contained a much higher proportion of radioactivity in hyaluronic acid than did the corresponding fractions of low-metastatic cell lines. The results provide a basis for further investigation of the potential role of hyaluronic acid in control of the behavior of epithelial tumor cells during metastasis.
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PMID:[Cell-matrix interactions involved in the process of tumor cell metastasis]. 671 65

Variant subpopulations of FM3A mouse mammary carcinoma cells that have increased lung-colonizing potential were obtained previously by sequentially harvesting pulmonary metastases, culturing their cells in vitro, and reestablishing the metastases in vivo. In the present study, glycosaminoglycan production by the parental and variant cells was studied after metabolic labeling of cultures by [14C]glucosamine for 24 hr. Analysis of the products indicated that the rate of incorporation of the labeled precursor into hyaluronic acid in the high-metastatic variant cells was 27 to 54 times the rate in the low-metastatic variant cells and that the increase in hyaluronic acid synthesis was not associated with an increase in the rate of synthesis of other glycosaminoglycans. Both the cell layers and media of high-metastatic variants contained a much higher proportion of radioactivity in hyaluronic acid than did the corresponding fractions of low-metastatic cell lines. The results provide a basis for further investigation of the potential role of hyaluronic acid in control of the behavior of epithelial tumor cells during metastasis.
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PMID:Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential. 682 5


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