Journal
MICROVASCULAR RESEARCH
Volume 82, Issue 3, Pages 318-325Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2011.06.011
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Funding
- Susan G. Komen [KG090860, RO1 CA72781]
- National Cancer Institute, National Institutes of Health [P30CA036727]
- Nebraska Research Initiative
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CXCR1 and CXCR2 are receptors for angiogenic ELR + CXC chemokines and are differentially expressed on endothelial cells; however, their functional significance in angiogenesis remains unclear. In this study, we determined the functional significance of these receptors in modulating endothelial cell phenotype by knocking-down the expression of CXCR1 and/or CXCR2 in human microvascular endothelial cells (HMEC-1) using short-hairpin RNA (shRNA). Cell proliferation, migration, invasion and capillary-like structure (CLS) formation were analyzed. Our data demonstrate that knock-down of CXCR1 and/or CXCR2 expression inhibited endothelial cell proliferation, survival, migration, invasion and CLS formation. Additionally, we examined the mechanism of CXCL8-dependent CXCR1 and/or CXCR2 mediated phenotypic changes by evaluating ERK phosphorylation and cytoskeletal rearrangement and observed inhibition of ERK phosphorylation and cytoskeletal rearrangement in HMEC-1-shCXCR1, HMEC-1-shCXCR2 and HMEC-1-shCXCR1/2 cells. Together, these data demonstrate that CXCR1 and CXCR2 expression plays a critical role in regulating multiple biological activities in human microvascular endothelial cells. (C) 2011 Elsevier Inc. All rights reserved.
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