Metastasis is the most devastating aspect of
cancer and it is the main cause of morbidity and mortality in
cancer patients.
Tumor cell adhesion to the vascular endothelial cell lining is an important step in metastatic progression and is prompted by platelets.
Mucin 1 is over-expressed and aberrantly glycosylated in more than 60% of pancreatic ductal adeno-
carcinomas, which mediate adhesion of
pancreatic cancer cells to platelets via
P-selectin. The
anticoagulant low molecular weight heparins (LMWHs), which are commonly used in venous Thromboprophylaxis and treatment, appear to have an effect on
cancer survival. The aim of this study is to investigate the effect of platelets on human
pancreatic cancer MPanc96 cell adhesion to the endothelial cell vessel wall, and to examine the effect of
heparin derivatives on MPanc96 adhesion using a novel, in vitro model of human umbilical cord vein. The modified
heparin S-NACH (sulfated non-
anticoagulant heparin), which is devoid of
antithrombin (AT) binding and devoid of inhibition of systemic AT-dependent
coagulation factors such as
factor Xa and IIa, and the
LMWH tinzaparin both potently reduced adhesion and invasion of fluorescence-labeled MPanc96
cancer cells to the endothelial layer of umbilical cord vein in a dose-dependent manner. S-NACH effectively inhibited
P-selectin mediated MPanc96 cell adhesion, and inhibited cell adhesion and invasion similar to
tinzaparin, indicating that systemic anticoagulation is not a necessary component for
heparin attenuation of
cancer cell adhesion, invasion, and
metastasis. Also, S-NACH and
tinzaparin versus
unfractionated heparin,
heparin derivatives
enoxaparin, deltaparin,
fraxiparin, and
fondaparinux were evaluated for their effect on platelet-
cancer cell adhesion. An in vivo anti-metastatic S-NACH-treated nude mouse model of MPanc96
pancreatic cancer cell
metastasis demonstrated potent anti-
metastasis efficacy as evidenced by IVIS imaging and histological staining.