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

被引：63

作者：

Bezuhly, Michael ^{[2
,3
]}

Cullen, Robyn ^{[1
]}

Esmon, Charles T. ^{[4
,5
]}

Morris, Steven F. ^{[2
,3
]}

West, Kenneth A. ^{[1
,6
,7
]}

Johnston, Brent ^{[1
,7
,8
]}

Liwski, Robert S. ^{[1
]}

机构：

[1] Dalhousie Univ, Dept Pathol, Halifax, NS B3H 1X5, Canada

[2] Dalhousie Univ, Dept Anat & Neurobiol, Halifax, NS B3H 1X5, Canada

[3] Dalhousie Univ, Dept Surg, Halifax, NS B3H 1X5, Canada

[4] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA

[5] Howard Hughes Med Inst, Oklahoma City, OK USA

[6] Dalhousie Univ, Dept Med, Halifax, NS B3H 1X5, Canada

[7] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 1X5, Canada

[8] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 1X5, Canada

来源：

BLOOD | 2009年 / 113卷 / 14期

关键词：

LIVER METASTASIS; GENE-EXPRESSION; P-SELECTIN; CELLS; EXTRAVASATION; INFLAMMATION; THROMBIN; GROWTH;

D O I：

10.1182/blood-2008-05-159434

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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-alpha mRNA levels. These findings support an important role for the aPC/EPCR pathway in reducing metastasis via inhibition of tumor cell adhesion and transmigration. (Blood. 2009;113:3371-3374)

引用

页码：3371 / 3374

页数：4

共 27 条

[1]

The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation [J].