Peptides inhibiting heparanase procoagulant activity significantly reduce tumour growth and vascularisation in a mouse model.
Thromb Haemost
; 116(4): 669-78, 2016 Sep 27.
Article
en En
| MEDLINE
| ID: mdl-27535490
ABSTRACT
Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway inhibitor (TFPI)-2, which inhibit heparanase procoagulant activity, were recently demonstrated to attenuate inflammation in a sepsis mouse model. The present study was designated to explore peptides effects on tumour growth and vascularisation. Cell lines of mouse melanoma (B16), mouse breast cancer (EMT-6), and human breast cancer (MDA-231) were injected subcutaneously to mice. Inhibitory peptides 5, 6 and 7 were injected subcutaneously in the area opposite to the tumour side. In the three tumour cell lines, peptides 5, 6 and 7 inhibited tumour growth and vascularisation in a dose-dependent manner, reaching a 2/3 reduction compared to control tumours (p<0.001). Additionally, a survival advantage (p<0.05) and reduced plasma thrombin-antithrombin complex (p<0.05) were observed in the treatment groups. Peptides delayed tumour relapse by six days and inhibited relapsed tumour size (p<0.001). In vitro, peptides did not inhibit tumour cell proliferation, migration or heparanase degradation of heparan sulfate chains, but significantly decreased tube formation. In conclusion, peptides inhibiting heparanase procoagulant activity significantly reduced tumour growth, vascularisation, and relapse. The procoagulant domain in heparanase protein may play a role in tumour growth, suggesting a new mechanism of coagulation system involvement in cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Melanoma Experimental
/
Glucuronidasa
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Thromb Haemost
Año:
2016
Tipo del documento:
Article