Selective antimetastatic effect of heparins in preclinical human melanoma models is based on inhibition of migration and microvascular arrest.
Use of heparin derivatives in several cancer types revealed that anticoagulant therapies have a beneficiary side effect: delay of tumor progression. Since there are no data on human melanoma, we have analyzed the effect of heparins in preclinical models. Neither unfractionated heparin (UFH), nor its low molecular weight derivative (LMWH) influenced in vitro or in vivo growth of HT168-M1 human melanoma cells. However, heparins significantly inhibited lung colony formation and liver metastasis development in the concentration range of 20-200 IU/kg, whereas recombinant hirudin was ineffective. The antimetastatic effect was due to an early (5-60 min) inhibition of tumor cell arrest in the lung microvasculature. Analysis of the molecular mechanism of the antimetastatic effect of heparins indicated a specific inhibition of tumor cell migration and matrix invasion. The presented experimental data suggest that heparins have specific antimetastatic effect in the case of human melanoma, which is independent from the coagulation cascade.
Bereczky
Bíborka
B
Department of Tumor Progression, National Institute of Oncology, Ráth Gy. u. 7-9, Budapest, 1122 Hungary.
Gilly
Réka
R
Rásó
Erzsébet
E
Vágó
Agnes
A
Tímár
József
J
Tóvári
József
J
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D002196:Capillaries / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000517:prevention & control* / Q000556:secondary*; D008175:Lung Neoplasms / Q000098:blood supply / Q000517:prevention & control* / Q000556:secondary*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000925:Anticoagulants; D016326:Extracellular Matrix Proteins; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin