Abstract
Engagement of endothelial protein C receptor (EPCR) by activated protein C (aPC) decreases expression of endothe-lial adhesion molecules implicated in tumor-endothelium interactions. We examined the role of the aPC/EPCR pathway on tumor migration and metastasis. In vitro, B16-F10 melanoma cells showed decreased adhesion to and transmigration through endothelium treated with recombinant human aPC (rhaPC). In murine B16-F10 metastasis models, transgenic EPCR overexpressing (Tie2-EPCR) mice exhibited marked reductions in liver (50%) and lung (92%) metastases compared with wild-type(WT) animals.Intravital imaging showed reduced B16-F10 entrapment within livers of Tie2-EPCR compared with WT mice. A similar reduction was observed in WT mice treated with rhaPC. Strikingly, rhaPC treatment resulted in a 44% reduction in lung metas-tases. This was associated with decreased lung P-selectin and TNF-α mRNA levels. These findings support an important role for the aPC/EPCR pathway in reducing metastasis via inhibition of tumor cell adhesion and transmigration.
| Original language | English |
|---|---|
| Pages (from-to) | 3371-3374 |
| Number of pages | 4 |
| Journal | Blood |
| Volume | 113 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Apr 2 2009 |
ASJC Scopus Subject Areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology