RT Journal Article
SR Electronic
T1 Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 82
OP 92
DO 10.1124/jpet.111.182055
VO 339
IS 1
A1 Yan Pan
A1 Tianluo Lei
A1 Bao Teng
A1 Jihong Liu
A1 Jianzhao Zhang
A1 Yu An
A1 Yuan Xiao
A1 Jing Han
A1 Xueyang Pan
A1 Junhua Wang
A1 Heming Yu
A1 Hong Ren
A1 Xuejun Li
YR 2011
UL http://jpet.aspetjournals.org/content/339/1/82.abstract
AB Low-molecular-weight heparin (LMWH) has been used in cancer patients with venous thromboembolic complications, resulting in a higher survival rate and an inhibitory action on experimental metastasis. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with LMWH for 24 h. We found that the resulting HUVECs could significantly inhibit the highly metastatic human prostate cancer cell line (PC-3M) in terms of its adhesion to the endothelium and migration across the endothelium, according to scanning electron microscopy. We also determined the elevated levels of endothelial intercellular Ca2+ concentration after the adhesion of PC-3M cells to HUVECs was greatly reduced by incubation with LMWH. Using proteomics, we surveyed the global protein changes in HUVECs after LMWH treatment and identified four down-regulated proteins that were possible isoforms of cytoskeletal vimentin intermediate filaments, cartilage-derived C-type lectin, and serine/threonine protein phosphatase 1β (PP-1B). LMWH affected the morphology of vimentin and the expression levels of αv integrin and PP-1B in HUVECs bound to PC-3M cells. Vimentin assists in the adhesion of PC-3M cells, which was confirmed by short interfering RNA experiments. Furthermore, the direct binding of purified vimentin protein with LMWH was detected with surface plasmon resonance methods. However, when we used fluorescence-labeled heparin for 24 h to identify whether this binding occurred within cells, heparin was distributed principally around endothelial cells. Taken together, these findings suggest that the monoincubation of LMWH with HUVECs could inhibit PC-3M cell adhesion to, and migration through, endothelium. LMWH's regulation of vimentin plays a role in the antimetastatic action.