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

A clone of B16 malignant melanoma cells with a preference for metastasis to the liver was isolated and characterized. The parent tumor cells (F1) were injected in the tail vein of C57BL/6 mice, and the resultant liver colonizing cells were isolated and then subcultured for two to three weeks. The cells were then reinjected into the next series of mice. After five such passages, a clone (L4) of melanoma cells was obtained that metastasized almost exclusively to the liver. A hepatic binding protein (HBP) was isolated from rabbit liver that agglutinated neuraminidase-treated F1 and L4 malignant melanoma cells. Different agglutination titers found between the parent and liver-metastasizing clone demonstrated differences in cell-surface properties between the parent tumor and the liver-metastasizing clone. These results demonstrate that malignant melanoma cells can be selected for preferential liver metastasis and can be recognized and agglutinated by specific HBPs. Metastasis from human uveal malignant melanoma may occur by similar mechanisms.
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PMID:Metastatic choroidal melanoma. Hepatic binding protein reactivity toward a liver-metastasizing clone. 684 70

Platelets are required for certain experimental tumor metastases and several lines of tumor cells have been shown to aggregate platelets. We have extracted a sedimentable sialolipoprotein, platelet aggregating material (PAM) from the cell surface of SV40 transformed Balb C3T3 fibroblasts which aggregates heparinized PRP at 2.5 micrograms/ml via the release reaction, following a one minute lag period. A similar extract from non-transformed 3T3 cells has barely measurable activity at 40 micrograms/ml. Gel-filtered platelets (GFP) do not aggregate with PAM. However, PAM aggregation can be restored by addition of 5% plasma but not by fibrinogen. Two plasma components are required: a heat-labile complement component which is activated during the lag period; and a heat-stable factor which is required for platelet aggregation. The pathophysiologic significance of PAM has been examined in ten variant cell lines derived from a spontaneously metastatic renal cell sarcoma of rats, initially induced with polyoma virus (PW20 Wistar-Furth parental lines). These lines were selected in vitro and in vivo from a single line and differed in their capacity to form distant tumors in various organs after subcutaneous injection. These cells were examined for cell surface sialylation, PAM and PAM sialic acid content, since cell surface sialic acid is increased in a variety of tumor tissues and PAM is inhibited by neuraminidase. A good correlation was obtained between in vivo metastatic potential and cell surface sialic acid, r = 0.83, p less than 0.003; cell surface sialic acid and PAM, r = 0.85, p less than 0.002; in vivo metastatic potential and sialic acid content of PAM, r = 0.69, p less than 0.03; and in vivo metastatic potential and PAM, r = 0.68, p less than 0.03. We conclude that platelets may play a role in hematogenous metastasis via the ability of tumor cells to aggregate platelets by cell surface constituents containing sialic acid. The platelet-tumor cell interaction requires activation of the alternate complement pathway and a heat stable plasma factor.
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PMID:Platelet aggregating material (PAM) of two virally-transformed tumors: SV3T3 mouse fibroblast and PW20 rat renal sarcoma. Role of cell surface sialylation. 711 9

A murine melanoma variant (B16-F10ir6), resistant to lymphocytic cytolysis, has been shown previously to produce lower numbers of tumor nodules in the lung of C57BL/6J mice following i.v. inoculations. These differences found in tumor implantation and lymphocyte recognition may be due to changes in surface properties of this cell line. Therefore, membrane-bound sialic acid (released by Vibrio cholerae neuraminidase treatment), ectosialyltransferase activity, and total cellular glycosidase levels were measured in this cell line and compared with levels in its parent melanoma tumor cell line, B16-F10, which was selected for its enhanced ability to form tumor nodules. The results of these studies indicate a correlation between the degree of lung implantation and the amount of tumor cell sialic acid accessible to neuraminidase cleavage, tumor cell surface sialyltransferase activity, and several cellular glycosidase activities. These results are consistent with the idea that membrane structural changes in the glycocalyx may account for the ability of a tumor cell to implant and metastasize.
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PMID:A correlation between cell surface sialyltransferase, sialic acid, and glycosidase activities and the implantability of B16 murine melanoma. 723 26

Platelets are required for certain experimental metastases. Several lines of animal tumor cells aggregate platelets in vitro and in vivo. Previous studies with one of these lines, an SV40-transformed 3T3 mouse fibroblast (SV3T3) have revealed that the platelet-aggregating material is an extractable membrane-associated sialolipoprotein which requires divalent cation, complement, and a heat-stable plasma component for activity. Little information is available on the interaction of human tumors with platelets. We now report on the ability of two human adenocarcinomas of the colon (LoVo and HCT-8) and an anaplastic mouse tumor (Hut-20) to aggregate platelets by a different mechanism, the generation of thrombin. These spontaneous cell lines aggregate human or rabbit platelet-rich plasma after a 1- to 2-min lag period. This is often followed by a visible clot. Unlike SV3T3 cells, aggregation by LoVo, HCT-8, and Hut-20 cells is not inhibited by neuraminidase, trypsin, or cobra venom factor. These three cell lines markedly shorten the recalcification time of citrated plasma, whereas SV3T3 cells do not. Phospholipase A2 treatment inhibits the shortening of the recalcification time for the three tumors; this parallels its inhibitory effect on platelet aggregation. LoVo, HCT-8, and Hut-20 cells generate thrombin via the "tissue factor" coagulation pathway (using coagulation factor-deficient substrates). Dansylarginine-N-(3-ethyl-1,5-pentanediyl)amide, a highly specific, potent antithrombin antagonist, inhibits LoVo-, HCT-8-, and Hut-20-induced platelet aggregation at 4 to 15 microM, whereas its effect on SV3T3 cells is negligible. If platelets are required for certain human tumor metastases, dansylarginine-N-(3-ethyl-1, 5-pentanediyl)amide, or other antithrombin agents, may prove to be valuable therapeutic agents.
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PMID:Inhibition of the platelet-aggregating activity of two human adenocarcinomas of the colon and an anaplastic murine tumor with a specific thrombin inhibitor, dansylarginine N-(3-ethyl-1,5-pentanediyl)amide. 730 74

Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg2+ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity: protein by trypsin; lipid by phospholipase A2 and non-ionic detergents; and sialic acid by neuraminidase. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
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PMID:Characterization of the platelet-aggregating activity of tumor cells. 735 51

The OPAR mouse monoclonal antibody (mAb) directed against rat hepatocytes was previously shown to inhibit adhesion of TA3/Ha mammary carcinoma cells to hepatocytes. The antigen is abundantly present at the surface of hepatocytes beneath the endothelium of liver capillaries where we have observed invasion of carcinoma cells to occur. The OPAR mAb reacted with three major bands on a Western blot of liver plasma membrane proteins. The same proteins were also seen upon immunoprecipitation from iodinated liver plasma membrane proteins. We have isolated OPAR antigens by lectin wheat germ agglutinin (WGA) and OPAR affinity chromatography. Amino acid sequence analysis revealed that two of the bands were alpha 1-macroglobulin and C4-binding protein, which are serum components produced by hepatocytes. The presence of the epitope on distinct proteins and our previous observation that it can be detected in the Golgi apparatus but not in the endoplasmic reticulum, suggested that OPAR reacts with a liver-specific glycoconjugate. Loss of OPAR reactivity after neuraminidase and N-glycosidase F treatment showed that the epitope contains sialic acid residues on N-linked sugar moieties. OPAR also reacted with rat fibronectin, and inhibited adhesion of TA3/St cells to fibronectin. This explains the inhibition by the OPAR mAb of TA3/St cell adhesion to hepatocytes, which we have shown to be due mainly to interaction with hepatocyte surface-associated fibronectin. However, adhesion of the related TA3/Ha cells to hepatocytes, which is mediated by the alpha 6 beta 4 integrin, and does not involve binding to fibronectin, is also inhibited. This suggests that alpha 6 beta 4 on liver-metastasizing carcinoma cells binds to an OPAR epitope-carrying glycoprotein produced by hepatocytes.
Clin Exp Metastasis 1995 Jan
PMID:Adhesion of carcinoma cells to rat hepatocytes and rat fibronectin is inhibited by the OPAR monoclonal antibody, which is directed against a rat liver-specific carbohydrate epitope. 752 66

Lectin-binding patterns of seven human melanoma clones and variants selected from the same parental cell line and differing in their spontaneous metastatic potential in an animal model were compared by flow cytometry and Scatchard analysis. Human melanoma clones and variants with high and low metastatic potential could be distinguished by their peanut agglutinin (PNA)-binding patterns, but not by their wheat germ agglutinin (WGA)-, Ulex europaeus agglutinin I (UEA I)-, and soybean agglutinin (SBA)-binding patterns. Low metastatic clones and variants proved to be made up of single poorly peanut agglutinin-binding cell population (2.20-3.52 x 10(6) sites/cell, Ka = 2.48-2.75 x 10(6) M-1). By contrast, highly metastatic variants were found to be constituted by two cellular subpopulations, exhibiting respectively a moderate 2.62-3.72 x 10(6) sites/cell) and a high peanut agglutinin staining (17.68-18.76 x 10(6) sites/cell). One highly metastatic clone was found to be homogeneously constituted by a single population of cells strongly binding this lectin (18.86 x 10(6) sites/cell) with an association constant of 4.06 +/- 10(6) M-1. Using an EPICS V cytometer, these two subpopulations were sorted from a highly metastatic variant and tested for their metastatic abilities: cells with high PNA binding generated a higher frequency of metastases than did moderately PNA-binding cells. Following treatment with Vibrio cholerae neuraminidase, all cells from all variants and clones were brightly labeled by PNA, collecting in a single peak with similar fluorescence intensities. Electrophoresis of total cellular proteins and subsequent detection with labeled PNA om Western blots show two major PNA-reactive glycoproteins with apparent molecular weights of 140 and 110 kDa (MAGP1 and MAGP2), expressed only in highly metastatic cells, but which can be strongly labeled by PNA in slightly metastatic cells following a treatment with neuraminidase. These results provide evidence that the expression of terminal galactose (beta 1-3)N-acetyl galactosamine structure, positioned on MAGP1 and MAGP2 glycoproteins, is associated with the metastatic potential of human melanoma cells.
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PMID:Expression of PNA-binding sites on specific glycoproteins by human melanoma cells is associated with a high metastatic potential. 817 91

The aim of this study was to establish a reproducible and quantitative liver metastasis model in mice. The in vitro colon 26 (C-26) cultured cell line was initially taken from an in vivo transplantable C-26 adenocarcinoma tumor mass using the standard enzymatic treatments, collagenase and DNAse. In vitro cultured cells x 10(4) were introduced into the portal vein of syngeneic BALB/c mice to induce liver metastases and, 3 weeks later metastatic foci were found in approximately 50% to 70% of the mice. In contrast, C-26 cells desialylated by neuraminidase (Nase) treatment greatly increased the incidence of hepatic metastases with countable hepatic colonies being found in all mice (100%). This result seems to be related to the liver-characteristic D-galactose receptors, since pre-injection with an excess amount of galactocerebroside completely prevented tumor colonization in the liver. Thus, although we cannot disregard the involvement of other adhesion molecules in this system as yet, our experimental model may become a useful tool for the analysis of hepatic metastases from colon cancer in the future.
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PMID:A successful liver metastasis model in mice with neuraminidase treated colon 26. 821 12

Pigmented hamster melanoma tumors growing in situ contain two subpopulations of melanoma cells that have different electrophoretic mobilities (EPM). A mild neuraminidase treatment, which removes sialic acid residues from the cell surface glycoproteins, reduces the EPM of both groups of melanoma cells yielding an electrophoretically uniform population. This shows that the differences in the EPM between the subpopulations of pigmented melanoma cells stem from the different content of sialic acid residues on the cell surface. The relationship between the different EPM melanoma cell subpopulations was, therefore, examined during tumor growth, development, and formation of metastases. The relative content of cells having high electrophoretic mobility, the "fast moving" cells, increases as the tumors grow larger. However, tumors of the same diameter contain nearly the same fraction of "fast moving" cells despite their age. The proportion of the "fast moving" cells is significantly higher in the central part than in the outermost layer of pigmented melanoma tumors. These data suggest that the development of "fast moving" cells is promoted by some size-dependent changes in the intratumor environment. In vivo selection of melanoma cells for their ability to colonize lungs renders tumors that reveal elevated metastatic potential and contain a significantly higher fraction of cells possessing high electrophoretic mobility than the parent tumor. Moreover, the metastatic nodules contain a remarkably elevated fraction of the "fast moving" cells. The reported correlation between the "fast moving" cell fraction and the metastatic potential suggests that the relative content of cells having high electrophoretic mobility may determine the metastaticity of pigmented hamster melanoma.
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PMID:Electrophoretic heterogeneity of pigmented hamster melanoma cells. 832 66

Nine monoclonal antibodies, lectin from Ulex europaeus and neuraminidase enzyme were employed to demonstrate the occurrence of type 1 and type 2 blood group antigens in 104 cases of papillary carcinoma of the thyroid. The reagents applied, recognize the following blood group related antigens: CA-50 (sialylated type 1 precursor), CA-19-9 (sialylated Le(a)), Le(a), Le(b), A, B, H, Le(x), sialylated Le(x), and Le(y). Immunohistochemical studies revealed that papillary carcinoma of the thyroid, in contrast to histologically normal thyroid tissue, is characterised by a progressive expression of blood group antigens. Most tumours (84%) reacted with C-50 antibody, whereas only a minority of the tissues demonstrated the CA-19-9 antigen (38%). Type 2 structures Le(x) (47%) and Le(y) (13%) were found less often than their corresponding type 1 isomers Le(a) (71%) and Le(b) (62%). Desialylation with neuraminidase increased the Le(a) and Le(x) staining intensity in 27 and 44 case, respectively. Of the A, B, H antigens the A determinants encountered most frequently (24%). Comparative examinations of sequential sections of the same tumour revealed coexpression of type 1 antigens in the same areas. In carcinomas showing type 1 and type 2 antigen reactivity, a complementary distribution of the structures in different tumour areas was often demonstrated. Some tumours presented combined type 1 and type 2 antigen expression in the same cells, however, in distinct areas within the cell. A follow-up examination was carried out in 68 of the 104 cases. The observation time ranged from 12 to 217 months. Thirteen patients suffered from recurrence, of which 7 died. While lymphatic metastases occurred in 39 tumours, distant metastases were detected in 6 patients. Most of the recurrences were found in patients with tumour classification pT4 (n = 19), whereas none of the pT1 carcinomas (n = 20) showed recurrence. The clinical results were compared to the blood group antigen expression results. There was no correlation between antigen expression and differentiation degree of the tumour. The pT4 tumours showed a significant higher expression of the CA-50, CA-19-9, Le(a) and Sialyl Le(x) structures. Carcinomas expressing the Le(y) antigen were associated with a significant higher level of metastasizing capacity. The Le(y), H type 1 and H type 2 antigens occurred more frequently in recurrent tumours (n = 14). In contrast, none of the patients whose carcinomas expressed the A-antigens (n = 14) suffered from a recurrence or hematogenous metastasis. Multiple stepwise regression analysis was carried out to check the importance of each staining and clinical factor. In this analysis, "distant metastasis' was the most important parameter, whereas the staining results were of minor statistical importance.
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PMID:[Blood group antigen expression in papillary carcinoma of the thyroid gland. An immunohistochemical and clinical study of expression of Lewis, ABO and related antigens]. 864 24


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