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 level of peripheral blood platelets was determined after i.v. injection of Corynebacterium parvum in normal C57BL mice and in those bearing the Lewis lung carcinoma. Twenty minutes after injection of a formalin-killed active strain (CN6134, (CN6134, which inhibited tumour metastases) or a killed inactive strain (CN 5888, which did not inhibit metastases) the number of circulating blood platelets was reduced by 50%. The level of platelets returned to control values by 8 h after the active, and by approximately 3 days after the inactive strain. The active strain alone caused a second and prolonged fall in platelet numbers, from approximately 16 h to 21 days after injection. Heparin given 3 X weekly to these mice restored the platelet count to normal values by 10 days after injection of active-strain C. parvum. The level of platelets in tumour-bearing mice was essentially similar to that in normal mice. Possible causes of the thrombocytopenia and the significance of platelets in metastasis are discussed.
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PMID:Effect of Corynebacterium parvum on peripheral blood platelets. 59 75

The present study of the effect of heparin and dextran 1000 on the metastasis formation after i.v. tumour cell injection in dextran non-sensitive rats using a syngeneic 20-methylcholanthrene induced fibrosarcoma showed that heparin treatment decreased with formation of pulmonary metastases in animals both untreated and treated with dextran 1000. Treatment with dextran 1000 increased the formation of pulmonary metastases in animals both untreated and treated with heparin and the effect of dextran 1000 was thus not affected by heparin treatment. Heparin did not have any direct action on the tumour cells, which influenced metastasis formation. The data suggest that heparin acts as an anticoagulant with decreased microthrombus formation around lodged cells and that dextrax 1000 stimulates metastasis formation primarily by mechanisms other than intravascular coagulation.
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PMID:Heparin, dextran 1000 and metastasis formation after I.V. tumour cell injection in dextran non-sensitive rats. 121 13

Tissue factor is a cell surface glycoprotein responsible for initiating the extrinsic pathway of coagulation. Many tumor cell homogenates and intact tumor cells have been shown to contain tissue factor activity. Immunohistochemical studies show that many tumors associated with Trousseau's syndrome express tissue factor on their cell surfaces. Tumor cells shed membrane fragments which carry tissue factor that can account for the activation of the clotting system. Tumor cells also produce soluble substances that can induce tissue factor expression on host cells, such as endothelium and monocytes, at sites distant from the tumor. Although, all the functional TF molecules are localized on the outer cell membrane in many tumor cells, the procoagulant activity on the intact cell surface is largely dormant and can be greatly enhanced upon cell injury or damage. Tissue factor procoagulant activity on the cell surface can be modulated by alterations in the plasma membrane without loss of cell viability. Tissue factor activity on cell surfaces is largely regulated by a plasma inhibitor, tissue factor pathway inhibitor. This inhibitor binds to both functional and non-functional tissue factor/VIIa complexes on the cell surface and prevents non-functional tissue factor/VIIa complexes from becoming functional after cell injury or lysis. Heparin, but not warfarin, therapy is effective in preventing the occurrence of devastating thrombotic events in patients with Trousseau's syndrome and the reason(s) for this are still unknown.
Cancer Metastasis Rev 1992 Nov
PMID:Tissue factor as a tumor procoagulant. 142 17

Fluid samples from brain tumour pseudocysts were examined for the presence of Fibroblast Growth Factor (FGF). Fluids were collected from 6 patients with differentiated low grade gliomas (group A), 3 anaplastic gliomas (group B) and 3 metastases (group C). For FGF assays pooled fluids from group A, B, and C were subjected to affinity chromatography on a Heparin-Sepharose column. Each pool contained endothelial cell mitogenic activity which eluted in the 1.2 M NaCl fraction and to a lesser degree in the 0.6 M fraction of Heparin-Sepharose high affinity chromatography. Mitogenic activity in the 1.2 M NaCl fraction of Heparin-Sepharose chromatography suggests the presence of acidic FGF (aFGF).
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PMID:Acidic fibroblast growth factor (aFGF) is present in the fluid of brain tumour pseudocysts. 170 57

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.
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PMID:Inhibition of tumor implantation at sites of trauma by plasminogen activators. 191 15

Proteins able to bind the iduronate containing glycosaminoglycans: heparin, heparan sulfate and dermatan sulfate, were detected in strongly (RMS 0) and weakly (RMS 8) metastatic rat rhabdomyosarcoma cell lines. The 35S-methionine-labeled proteins solubilized from the cell membranes were chromatographed on Heparin-Ultrogel affinity column. The main retained protein migrated with an apparent molecular size of 19 kDa on polyacrylamide gel electrophoresis from both cell lines. The 19 kDa protein exhibited a higher affinity for iduronate containing glycosaminoglycans than for the glucuronate containing chondroitin sulfates. It was immunologically distinct from acid and basic fibroblast growth factors. The membranes of the RMS 8 cells contained about a two times higher amount of labeled 19 kDa protein than the membranes of the RMS 0 cells. The decreased amount of the labeled heparin-binding proteins in the highly metastatic cell line is in agreement with the previously evidenced decreased receptor-mediated binding of the iduronate containing glycosaminoglycans by these cells.
Invasion Metastasis 1991
PMID:Heparin-binding sites of rat rhabdomyosarcoma cells with low and high metastatic capacity. 193 76

We have investigated the effect of sulfated chitin derivatives on the intravascular events in the metastatic cascade. 6-O-Sulfated carboxymethyl chitin (SCM-chitin III), as well as heparin, significantly inhibited the arrest of B16-BL6 cells in lungs after co-injection with radiolabeled tumor cells, but carboxymethylated chitin (CM-chitin) had no effect. Heparin showed a potent inhibitory effect on tumor cell-elicited platelet aggregation and on blood coagulation, which can subsequently enhance the survival, arrest and invasiveness of tumor cells, whereas SCM-chitin III showed much weaker properties. In contrast, SCM-chitin III was found to inhibit the adhesion of tumor cells to subendothelial matrix, while heparin did not. SCM-chitin III was still active in inhibiting experimental lung metastasis even in mice which had been pretreated with anti-asialo GM1 serum or carrageenan to eliminate NK cells or macrophages. Thus, these results suggest that SCM-chitin-mediated inhibition of tumor metastases is distinct from that by heparin and may be due to interference with tumor cell arrest in the capillaries and consequently to the inhibition of tumor cell adhesion to subendothelial matrix.
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PMID:Inhibition of tumor cell arrest in lungs by antimetastatic chitin heparinoid. 211

Heparan sulfate (HS) enhanced the growth of the highly metastatic (HM) 3LL cell line, but not that of the low metastatic (LM) counterpart, in a dose-dependent way. Heparin, chondroitin sulfate, hyaluronate did not produce this effect. At 4 degrees C both cell lines exhibited high affinity binding sites (Kd 10(-8) M) for exogenous HS. Unlike LM cells, the HM ones lost half of the surface-bound HS during the 24-hour incubation at 37 degrees C. HM cells in the exponential growth phase took up the bound HS at lower rate than the LM counterparts. Both cell lines fragmented the exogenous HS intracellularly, but only the HM cells were able to degrade it at the cell surface. The HM cells contained much more heparin-binding proteins--especially in the cell membrane and nuclear fraction--than the LM ones. These results clearly demonstrate that the interactions of tumor cells with exogenous HS are influenced by the invasive phenotype. We suggest also that there could be a correlation between the surface degradation, the slow uptake and the growth-promoting effect of the exogenous HS.
Invasion Metastasis 1990
PMID:Interactions of exogenous heparan sulfate with tumor cells of different metastatic phenotype. 222 18

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

A combination of heparin and cortisone acetate significantly inhibited both embryonic angiogenesis and the tumor growth of Lewis lung carcinoma (3LL) transplanted into C57BL/6 mice, although each of these agents used alone affected neither angiogenesis nor tumor growth. On the other hand, this combination neither decreased the number of metastatic foci in the lung nor prolonged the survival time of mice with 3LL. All tumor-bearing mice died of hemothorax due to pulmonary metastases. Cortisone acetate by itself increased metastasis, and addition of heparin did not affect accelerated metastasis. Because an antiangiogenic activity appears independent of metastasis acceleration by cortisone acetate, the use of steroids other than cortisone acetate having no metastasis-promotion effect should be required for an antiangiogenic tumor therapy in the presence of heparin. Heparin plus cortisone acetate prevented the DNA synthesis of cultured vascular endothelial cells but not that of cultured 3LL cells. Additionally, oral administration of this combination decreased the [3H]thymidine labeling of endothelial cells of tumor blood vessels prior to the suppression of tumor growth. The specific inhibition of the growth of endothelial cells by heparin plus cortisone acetate was revealed in both the in vitro and the in vivo tests.
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PMID:Inhibitory effects of heparin plus cortisone acetate on endothelial cell growth both in cultures and in tumor masses. 243 5


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