Inhibition of osteolytic bone metastasis by unfractionated heparin.
In the current study, we examine heparin's anti-metastatic properties by using a well-defined mouse model of osteolytic bone metastasis. C57BL/6 mice were treated with increasing doses of unfractionated heparin (15, 20, or 25 units/mouse) 30 min prior to the left ventricular injection of GFP-transfected B16F10 melanoma cells. Heparin's effect on tumour burden and bone strength was then quantified 14 days later by bone histomorphometry and biomechanical testing, respectively. Based on histomorphometric analysis of the femurs, injection of GFP-transfected melanoma cells resulted in a 37% decrease in cancellous bone volume and a 68% increase in osteoclast surface. This was associated with a 13% reduction in bone strength as measured by biomechanical testing. However, when the mice were first pre-treated with 25 units of heparin, tumour burden was decreased by 73% and tumour cell-dependent decreases in both cancellous bone volume and bone strength were prevented. Based on these observations, we conclude that heparin inhibits the ability of tumour cells to metastasize to bone and that as such, prevents tumour cell-induced decreases in bone strength.
Yee
Colin K
CK
Department of Pathology and Molecular Medicine, McMaster University and the Henderson Research Center, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3.
Butcher
Martin
M
Zeadin
Melec
M
Weitz
Jeffrey I
JI
Shaughnessy
Stephen G
SG
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D015519:Bone Density / Q000502:physiology; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005269:Femur / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis; D047368:Tumor Burden
D000925:Anticoagulants; D049452:Green Fluorescent Proteins; D006493:Heparin