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

Blood platelets have been suggested to play an important role in modulating the development of experimental metastases. Tumour cells can induce platelet aggregation in vitro and a number of mechanisms have been proposed to explain the in vivo and in vitro observations. In the present study, we used tumour cells cloned from B16 melanoma and mouse mammary tumour virus (MMTV) carcinoma polyclonal populations to check whether tumour cells with low- and high-metastatic behaviour in vivo had different quantitative and qualitative platelet-aggregating activity in vitro. We found no significant quantitative difference between platelet aggregation induced by the low- and the high-metastatic clones. Indeed both the high and the low metastatic B16 melanoma clones poorly aggregated platelets, while both the high and low metastatic MMTV carcinoma clones efficiently aggregated platelets. Both the B16 melanoma and the MMTV carcinoma parental cell lines, which can be classed as intermediate metastatic, aggregated platelets well. However, based on the results with heparin and creatine phosphate/creatine phosphokinase, it appeared that qualitative differences might exist in the mechanism of platelet aggregation by tumour cells. For the parental lines and highly metastatic clone C1 a thrombin-linked component was more important than an ADP-like component, which was nevertheless present, to promote platelet aggregation. For the low-metastatic clone C2, the ADP-like component appeared to be the most important.
Invasion Metastasis 1987
PMID:Tumour-cell-induced platelet aggregation: studies with cloned metastatic and non-metastatic variants. 367 44

Twenty-four patients with various types of tumors and without evidence of consumption coagulopathy (normal routine coagulation tests) were investigated for intraplatelet ATP, ADP, serotonin, beta-thromboglobulin and platelet factor 4; the percentage of light circulating platelets was also determined. Evidence for an acquired storage pool defect was found in seven patients (29%) without any correlation with the clinical status, the presence of metastases, platelet count or fibrinogen level. These results show that exhausted platelets are commonly encountered in cancerous patients even in the absence of consumption coagulopathy. The precise mechanism of this abnormality remains to be established.
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PMID:Exhausted platelets in patients with malignant solid tumors without evidence of active consumption coagulopathy. 623 14

This review studies interactions of tumor cells with a particular host system which is normally responsible for hemostasis and the physiological integrity of the blood vessel luminal surface. With malignancy components of this system are frequently activated, producing abnormalities of blood coagulation, increased platelet responses, and conditions favoring tumor growth and metastasis. Activation of the clotting cascade is mediated by tumor and macrophage procoagulants, acting via Factor X or VII. Thrombin and fibrin are formed. Thrombin also interacts with platelets and the endothelium, potentiating or decreasing coagulation. Generation of thrombin or other tumor mechanisms activate platelets, leading to direct aggregation or secretion of ADP, serotonin, and/or intermediates of the arachidonate metabolism. Vascular lesions caused by tumor attack, platelet secretion, or exogenous agents promoting metastasis may also activate the hemostatic system. It is not yet fully understood how activation of the clotting system, including platelets, contributes to metastasis. Secretion of platelet products appears, however, to be heavily involved. Based on putative mechanisms of action, anticoagulants, platelet inhibitors, thrombocytopenic or vascular repairing agents have been used to control tumor spread. Results depended on the agent and experimental model of metastasis used. Except for coumarin, which was beneficial even against spontaneous metastases, other anticoagulants and platelet inhibitors, excluding perhaps Nafazatrom, gave equivocal results. Thrombocytopenic agents, however, were effective in every tumor system and with any experimental model of metastasis, indicating that platelets play a role in this process. Also consistent were the inhibitory effects of leech salivary gland extract (probably a vascular repairing agent) against lung tumor colonization promoted by ionizing radiation, cyclophosphamide, and cortisone.
Cancer Metastasis Rev 1984
PMID:Role of plasma, platelets, and endothelial cells in tumor metastasis. 638 44

The mechanisms by which B16, 3LL and MH134 tumor cells induce platelet aggregation were studied. The B16 and 3LL tumors, which have high or moderate procoagulant activities, aggregated platelets only in the presence of Ca2+ and plasma factors. MH134, which had much lower procoagulant activity, aggregated platelets even in the absence of these factors. The induction of aggregation by B16 and 3LL could be prevented by thrombin inhibitors but not by the ADP scavenger, suggesting that thrombin, generated by procoagulant activities of tumor cells themselves, might play a major role in initiating aggregation. MH134-induced aggregation was not affected by any of the inhibitors, indicating that the mechanisms by which MH134 initiate platelet aggregation are independent of both thrombin and ADP.
Invasion Metastasis 1984
PMID:Platelet-aggregating activities of metastasizing tumor cells. II. Variety of the aggregation mechanisms. 648 Feb 87

We have examined the effects on platelet function of two sublines (M4 and M9) derived from spontaneous lung nodules of a benzopyrene-induced murine fibrosarcoma (m FS6). The subline M4 was more metastatic and the subline M9 less metastatic than the primary tumour. Only the more malignant cells were able to induce irreversible aggregation of human platelets; this effect was concentration-dependent and was associated with the release of serotonin by platelets. Both aggregation and release were inhibited by preincubation of platelets with ASA, not by preincubation of the cells. The supernatants of cell suspensions had no aggregating activity. However, the neoplastic cells in culture media released an activity directly stimulating platelet aggregation and potentiating the platelet response to ADP; again, this activity was higher for the more malignant cells and the effects were inhibited by preincubation of platelets with ASA. These results suggest a role for platelets in the development of tumour metastases.
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PMID:Interactions between neoplastic cells with different metastasizing capacity and platelet function. 668 86

The role of platelets in cancer metastasis was studied by investigating the effects of the antiplatelet agents ticlopidine, diltiazem, dipyridamole and trapidil on artificial and spontaneous pulmonary metastases in mice. These agents were tested at their optimal inhibitory doses on adenosine diphosphate-induced platelet aggregation; namely, 100 mg/kg for ticlopidine, 2 mg/kg for diltiazem, 180 mg/kg for trapidil and 60 mg/kg for dipyridamole. At these doses, trapidil caused moderate inhibition of thrombin-induced platelet aggregation in mice, but the other agents had only slight effects. Artificial pulmonary metastasis was produced by inoculation of Lewis lung carcinoma (LLC) or B16 melanoma (B16) cells into C57BL/6 mice. For induction of spontaneous pulmonary metastases, these tumor cells were implanted subcutaneously into the footpads of mice. The resulting primary tumors of LLC and B16 were removed 9-10 and 17 days later, respectively. Artificial pulmonary metastases were inhibited significantly by all the antiplatelet agents tested. Spontaneous pulmonary metastases were markedly reduced only when these agents were given after removal of the primary tumor. The role of platelets is discussed with respect to thrombus formation in the lodgement of tumor cells and the participation of platelet-derived growth factor in the growth of metastatic foci.
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PMID:Effects of antiplatelet agents on pulmonary metastases. 672 29

The effects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on collagen- and ADP-induced human platelet aggregation are investigated. Platelet rich plasma (PRP) and platelet poor plasma (PPP) from healthy male and female donors were used. The PRP was adjusted with analogous PPP to 300,000 platelets/microliters. Platelet aggregation was studied according to Born's turbidimetric technique using an Aggrecorder II PA 3220 with collagen at a concentration of 10 micrograms/ml and ADP at a concentration of 30 microM. Vincristine, doxorubicin and epirubicin significantly (p < 0.01) inhibited collagen- and ADP-induced platelet aggregation. The vincristine induced inhibition was higher than that induced by doxorubicin or epirubicin. The effects of doxorubicin and epirubicin were more intense on ADP-induced platelet aggregation than on the collagen induced one. Moreover, the doxorubicin inhibition of ADP-induced platelet aggregation was greater than the epirubicin one. In conclusion, our study shows that vincristine, doxorubicin and epirubicin inhibit human platelet aggregation. The present results may improve the therapeutic use of these drugs since it has been clearly shown that drugs with antiplatelet activity could block metastases.
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PMID:Effects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on human platelet aggregation. 793 Sep 57

DN-9693, c-AMP: phosphodiesterase inhibits platelet aggregation induced by metastasizing tumor cells and blood-borne metastases of these tumors. Effects of this drug on pulmonary metastases was studied in wKA rats, which were sc implanted with 4-dimethylaminoazobenzene (DAB) induced KDH-8 tumor cells. KDH-8 cells (10(5)) were sc inoculated on day 0 and excised on day 20. DN-9693 was ip injected at a dose of 150 micrograms twice a day for 7 days pre operatively (-7 - 0) or perioperatively (-3 - +3) or postoperatively (0 - +7). The rats were sacrificed on day 20 after surgery, and lung weight and the number of surface pulmonary nodules were measured. Both were significantly decreased in the group of perioperative and postoperative administration of DN-9693. The survival of these rats were furthermore prolonged when Cyclophosphamide (40 mg/kg) was sc injected 3 days after surgical resection. KDH-8 tumor cells (10(4)) were iv inoculated on day 0, and DN-9693 was ip injected at a dose of 150 micrograms twice a day for 7 days on day 0 approximately 7. Rats were sacrificed on day 20, and same studies as above were done. In this artificial pulmonary metastases, the decrease of the number of lung nodules was observed in WKA rat treated with DN-9693. Platelet aggregation induced by KDH-8 tumor cells was inhibited by ADP inhibitor (apyrase, CP/CPK) and thrombin inhibitor (heparin, MD-805); KDH-8 tumor cells induced platelet aggregation by two different mechanisms: ADP-mediated aggregation and thrombin-mediated aggregation. This platelet aggregation by KDH-8 tumor cells was inhibited by DN-9693 with dose-dependency. DN-9693 had no direct anti-tumor effects either in vivo or in vitro. The results indicates that this drug prevents pulmonary metastases by inhibiting platelet aggregation.
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PMID:[Effects of platelet aggregating inhibitor on pulmonary metastases of tumor cells after surgical resection]. 822 73

In this study, we examined the effect of triflavin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, on human cervical carcinoma (HeLa) cell- and B16-F10 mouse melanoma cell-induced platelet aggregation (TCIPA) in heparinized platelet-rich plasma. TCIPA appears to play an important role in the development of certain experimental tumor metastases. Two ADP-scavenging agents, apyrase (10 U/ml) and creatine phosphate (CP) (5 mM)/creatine phosphokinase (CPK) (5 U/ml) completely inhibited B16-F10 TCIPA, but hirudin (5 U/ml) had no effect. In contrast, apyrase and CP/CPK did not inhibit HeLa TCIPA while hirudin completely inhibited it. Furthermore, HeLa cells initially induced platelet aggregation and then blood coagulation at a later stage. In addition, HeLa cells shortened, in a concentration-dependent manner, the recalcification time of normal as well as factor VIII- and IX-deficient human plasma, but did not affect the recalcification time of factor VII-deficient plasma. This suggests that HeLa TCIPA occurs via activation of the extrinsic pathway, probably owing to tumor cell expression of tissue factor-like activity. HeLa cell-induced thrombin generation was confirmed by detection of amidolytic activity towards a chromogenic substrate, S-2238 (H-D-Phe-Pip-Arg-p-NA). Triflavin and GRGDS inhibited, in a dose-dependent manner, TCIPA caused by either cell line. On a molar basis, triflavin was 10,000-30,000 times more potent than GRGDS in this regard. Moreover, monoclonal antibodies raised against glycoprotein (GP) IIb/IIIa complex (i.e., 7E3 and AP2) and against GP Ib (i.e., AP1) completely inhibited HeLa TCIPA. 7E3 and AP2 inhibited B16-F10 TCIPA by up to 80% whereas AP1 showed only 30% inhibition of B16-F10 TCIPA. In conclusion, the inhibitory effect of triflavin on HeLa and B16-F10 TCIPA may be mediated principally by the binding of triflavin to the fibrinogen receptor associated with GP IIb/IIIa complex on the platelet surface. However, GP Ib is also involved in HeLa TCIPA as thrombin formation is the key factor in triggering platelet aggregation caused by HeLa cells.
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PMID:Triflavin, an Arg-Gly-Asp-containing peptide, inhibits tumor cell-induced platelet aggregation. 822 81

T-cell hybridomas are highly metastatic, and their in vitro invasiveness correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT), which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided evidence that the PT-sensitive signal stimulates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent. In the present study, we have transfected the cDNA of the PT ADP-ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function permanently. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP-ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free. Metastasis to the liver was almost completely prevented and less metastases were formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases occurred with a frequency similar to that of controls. We conclude that G1-proteins play an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues.
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PMID:Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T-cell hybridoma reduces metastatic capacity. 887 11


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