Chemokine Receptor CXCR7 Is a Functional Receptor for CXCL12 in Brain Endothelial Cells
| العنوان: | Chemokine Receptor CXCR7 Is a Functional Receptor for CXCL12 in Brain Endothelial Cells |
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| المؤلفون: | Kevin A. Walter, Yang Liu, Eleanor B. Carson-Walter |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 8, p e103938 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Time Factors, Tumor Physiology, lcsh:Medicine, Small hairpin RNA, Chemokine receptor, Cell Movement, Basic Cancer Research, Medicine and Health Sciences, lcsh:Science, Receptor, Neurological Tumors, Tube formation, Gene knockdown, Multidisciplinary, Chemotaxis, Brain, Glioma, 3. Good health, Cell biology, Cell Motility, Neurology, Oncology, Gene Knockdown Techniques, RNA Interference, Signal transduction, Chemokines, Research Article, Signal Transduction, Neovascularization, Physiologic, Vascular Cell Adhesion Molecule-1, Biology, Cell Line, Tumor, Cell Adhesion, Humans, Cell adhesion, Molecular Biology, Cell Proliferation, Receptors, CXCR, Matrigel, Tumor Necrosis Factor-alpha, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Endothelial Cells, Cell Biology, Chemokine CXCL12, Tumor Vasculature, Immunology, Microvessels, lcsh:Q |
| الوصف: | The chemokine CXCL12 regulates multiple cell functions through its receptor, CXCR4. However, recent studies have shown that CXCL12 also binds a second receptor, CXCR7, to potentiate signal transduction and cell activity. In contrast to CXCL12/CXCR4, few studies have focused on the role of CXCR7 in vascular biology and its role in human brain microvascular endothelial cells (HBMECs) remains unclear. In this report, we used complementary methods, including immunocytofluorescence, Western blot, and flow cytometry analyses, to demonstrate that CXCR7 was expressed on HBMECs. We then employed short hairpin RNA (shRNA) technology to knockdown CXCR7 in HBMECs. Knockdown of CXCR7 in HBMECs resulted in significantly reduced HBMEC proliferation, tube formation, and migration, as well as adhesion to matrigel and tumor cells. Blocking CXCR7 with a specific antibody or small molecule antagonist similarly disrupted HBMEC binding to matrigel or tumor cells. We found that tumor necrosis factor (TNF)-α induced CXCR7 in a time and dose-response manner and that this increase preceded an increase in vascular cell adhesion molecule-1 (VCAM-1). Knockdown of CXCR7 resulted in suppression of VCAM-1, suggesting that the reduced binding of CXCR7-knockdown HBMECs may result from suppression of VCAM-1. Collectively, CXCR7 acted as a functional receptor for CXCL12 in brain endothelial cells. Targeting CXCR7 in tumor vasculature may provide novel opportunities for improving brain tumor therapy. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e090ae31778dfa55c52a56d6465c13fTest http://europepmc.org/articles/PMC4118981Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2e090ae31778dfa55c52a56d6465c13f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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