LMWH Bemiparin and ULMWH RO-14 Reduce the Endothelial Angiogenic Features Elicited by Leukemia, Lung Cancer, or Breast Cancer Cells

Abstract

Low-molecular-weight heparins (LMWH) are anticoagulant drugs that also possess antitumor properties. We evaluated whether “second generation” LMWH bemiparin and the Ultra-Low-MWH (ULMWH) RO-14 are able to inhibit in vitro the angiogenic response of microvascular endothelium stimulated by tumor-cell-conditioned media (TCM) from human leukemia, lung cancer, and breast cancer cells. Bemiparin and RO-14 dose dependently inhibited the increase of capillary-like tube formation (Matrigel-based assay) and endothelial migration (wound-healing assay) induced by TCM. Both drugs also inhibited angiogenic response elicited by purified VEGF and FGF-2. These findings support a possible role of these molecules as adjuvant drugs in cancer treatment.

Keywords: :

• Heparins
• LMWH
• Angiogenesis
• Endothelial cells
• Cancer cells

ACKNOWLEDGMENTS

This study has been supported by an unrestricted grant from Laboratorios Farmacéuticos ROVI, and by a grant from the Italian Ministry of Health (Grant “Oncological Research” no. 29/07).