PMID- 16132580 OWN - NLM STAT- MEDLINE DCOM- 20051018 LR - 20220318 IS - 0262-0898 (Print) IS - 0262-0898 (Linking) VI - 22 IP - 1 DP - 2005 TI - Selective antimetastatic effect of heparins in preclinical human melanoma models is based on inhibition of migration and microvascular arrest. PG - 69-76 AB - 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. FAU - Bereczky, Biborka AU - Bereczky B AD - Department of Tumor Progression, National Institute of Oncology, Rath Gy. u. 7-9, Budapest, 1122 Hungary. FAU - Gilly, Reka AU - Gilly R FAU - Raso, Erzsebet AU - Raso E FAU - Vago, Agnes AU - Vago A FAU - Timar, Jozsef AU - Timar J FAU - Tovari, Jozsef AU - Tovari J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Clin Exp Metastasis JT - Clinical & experimental metastasis JID - 8409970 RN - 0 (Anticoagulants) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Heparin, Low-Molecular-Weight) RN - 9005-49-6 (Heparin) SB - IM MH - Animals MH - Anticoagulants/pharmacology/*therapeutic use MH - Capillaries/drug effects MH - Cell Proliferation/drug effects MH - Extracellular Matrix Proteins/metabolism MH - Female MH - Hemostasis/drug effects MH - Heparin/pharmacology/*therapeutic use MH - Heparin, Low-Molecular-Weight/pharmacology/therapeutic use MH - Humans MH - Liver Neoplasms/blood supply/*prevention & control/*secondary MH - Lung Neoplasms/blood supply/*prevention & control/*secondary MH - Melanoma/*drug therapy/*pathology MH - Mice MH - Mice, SCID MH - Neoplasm Transplantation MH - Neoplastic Stem Cells/drug effects/metabolism MH - Tumor Cells, Cultured EDAT- 2005/09/01 09:00 MHDA- 2005/10/19 09:00 CRDT- 2005/09/01 09:00 PHST- 2004/11/16 00:00 [received] PHST- 2005/03/14 00:00 [accepted] PHST- 2005/09/01 09:00 [pubmed] PHST- 2005/10/19 09:00 [medline] PHST- 2005/09/01 09:00 [entrez] AID - 10.1007/s10585-005-3859-6 [doi] PST - ppublish SO - Clin Exp Metastasis. 2005;22(1):69-76. doi: 10.1007/s10585-005-3859-6.