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Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin
- Source :
- Thrombosis Research. 121:637-645
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Clinical studies suggest a survival advantage in cancer patients receiving low molecular weight heparin (LMWH). A suggested mechanism for this beneficial effect may reside in the antiangiogenic activity of heparins.In this study we investigated whether two different LMWHs, i.e. enoxaparin and dalteparin, and unfractionated heparin (UFH), affect the angiogenic potential of human microvascular endothelial cells (HMEC-1) promoted by tumor cells.HMEC-1 cells were incubated with tumor cell conditioned media (TCM) derived from human breast cancer and leukemic cells (i.e. MCF-7, MDA.MB.231, and NB4 cell lines) or recombinant cytokines (i.e. VEGF, FGF-2, TNF-alpha) +/-heparins. Capillary-like tube formation in Matrigel and cell proliferation were evaluated.All three TCM induced a significant (p0.05) increase in total length of tubes formed by HMEC-1 in Matrigel. These increases were significantly counteracted (62 to 100% mean inhibition) by enoxaparin and dalteparin, but were significantly less affected by UFH. Similarly, the tube formation induced by standard VEGF, FGF-2, or TNF-alpha was 100% inhibited by enoxaparin, and 70-90% by dalteparin, whereas minor or no inhibition was observed with UFH. VEGF was the most active cytokine in TCM of both breast cancer and leukemic cells. EC proliferation was significantly increased by standard angiogenic factors, and slightly affected by breast cancer TCM (p=ns). The addition of heparins significantly counteracted the proliferative stimuli.These results support a major role for LMWH compared to UFH in inhibiting the proangiogenic effect exerted by tumor cells or purified angiogenic factors on microvascular endothelium.
- Subjects :
- Vascular Endothelial Growth Factor A
medicine.medical_specialty
Angiogenesis
Angiogenesis Inhibitors
Pharmacology
chemistry.chemical_compound
Neoplasms
Internal medicine
Tumor Cells, Cultured
medicine
Humans
Cell Proliferation
Tube formation
Matrigel
Dalteparin sodium
Heparin
Cell growth
business.industry
Endothelial Cells
Hematology
Heparin, Low-Molecular-Weight
Capillaries
Endothelial stem cell
Vascular endothelial growth factor
Endocrinology
chemistry
business
medicine.drug
Subjects
Details
- ISSN :
- 00493848
- Volume :
- 121
- Database :
- OpenAIRE
- Journal :
- Thrombosis Research
- Accession number :
- edsair.doi.dedup.....05f058406d3ac6c9637fbaf64138e7ec