Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis

被引：106

作者：

Wente, Moritz N.

Keane, Michael P.

Burdick, Marie D.

Friess, Helmut

Buechler, Markus W.

Ceyhan, Gueralp O.

Reber, Howard A.

Strieter, Robert M.

Hines, Oscar J.

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Gastrointestinal Surg Sect, Div Gen Surg, Los Angeles, CA 90095 USA

[2] Univ Heidelberg, Dept Gen Surg, Heidelberg, Germany

[3] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA

来源：

CANCER LETTERS | 2006年 / 241卷 / 02期

关键词：

pancreatic cancer; CXC chemokines; angiogenesis; corneal neovascularisation; immunohistochemistry;

D O I：

10.1016/j.canlet.2005.10.041

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A central feature of all solid tumor growth is the presence of neovascularization. The CXC chemokines GRO-gamma/CXCL3, ENA-78/CXCL5, and IL-8/CXCL8 have profound angiogenic potential mediated through the CXCR2 receptor. The aim of the present study was to evaluate the expression of the angiogenic chemokines in three human pancreatic cancer cell lines and to determine the role of these proteins in pancreatic cancer angiogenesis. Secreted CXC protein levels in the supernatant of the cell lines were analyzed by ELISA. A rat corneal micropocket model was used to determine the angiogenic potential of these secreted CXC chemokines in vivo. ELISA confirmed expression of all three tested CXC chemokines in the supernatant of two cell lines. In the corneal micropocket assay, neovascularization was induced using pelleted supernatant of all three-cell lines. Using an anti-CXCR2 antibody, neovascularization was significantly inhibited in the high expressing BxPC-3 cell line samples. In addition, the expression of ENA-78/CXCL5 and IL-8/CXCL8 has been evaluated in human pancreatic cancer tissue samples by using immunohistochemistry in order to further investigate the potential role of CXC chemokines in pancreatic cancer angiogenesis and tumorigenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：221 / 227

页数：7

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