Characterization of the CXCR4 signaling in pancreatic cancer cells

被引：54

作者：

Billadeau D.D. ^{[2
,5
]}

Chatterjee S. ^{[1
]}

Bramati P. ^{[3
]}

Sreekumar R. ^{[4
,5
]}

Shah V. ^{[1
]}

Hedin K. ^{[3
]}

Urrutia R. ^{[1
,5
,6
,7
]}

机构：

[1] Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic College of Medicine, Rochester

[2] Oncology Research Department, Mayo Clinic College of Medicine, Rochester

[3] Department of Immunology, Mayo Clinic College of Medicine, Rochester

[4] Department of Endocrinology, Mayo Clinic College of Medicine, Rochester

[5] Tumor Biology Program, Mayo Clinic College of Medicine, Rochester

[6] Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester

[7] Gastroenterology Research Unit, Saint Mary's Hospital, 2-445 Alfred Bldg., Rochester

来源：

Journal of Gastrointestinal Cancer | 2006年 / 37卷 / 4期

关键词：

Angiogenesis; CXCL12; CXCR4; ERK; Pancreatic cancer;

D O I：

10.1007/s12029-007-0011-7

中图分类号：

学科分类号：

摘要：

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease. © 2007 Humana Press Inc.

引用

页码：110 / 119

页数：9

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