Details

Autor(en) / Beteiligte

• Bezuhly, Michael
• Cullen, Robyn
• Esmon, Charles T.
• Morris, Steven F.
• West, Kenneth A.
• Johnston, Brent
• Liwski, Robert S.

Titel

Role of activated protein C and its receptor in inhibition of tumor metastasis

Ist Teil von

• Blood, 2009-04, Vol.113 (14), p.3371-3374

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2009

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Engagement of endothelial protein C receptor (EPCR) by activated protein C (aPC) decreases expression of endothelial 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 metastases. 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.