| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Cancer Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121;
Veterans Affairs Medical Center/University of California, San Diego, CA 92161; and
Department of Internal Medicine, University of Freiburg, Freiburg, Germany
Microvascular endothelial cells (HMECs) express both the CXCR1 and the CXCR2, but cell migration is almost entirely mediated by the CXCR2. Similarly, NIH 3T3 cells transfected with the CXCR2 migrated toward IL-8, whereas CXCR1-transfected cells failed to do so. This situation differs from that seen in leukocytes, where chemotaxis is primarily a function of the CXCR1. To define signal transduction pathways that explain this difference in behavior, various inhibitors were used to block cell migration. Apart from inhibitors of phosphatidylinositol 3-kinase, which blocked migration in all cases, inhibition of the epidermal growth factor (EGF) receptor blocked IL-8-mediated cell migration in HMECs and in CXCR2-transfected NIH 3T3 cells, but not in RBL2H3 cells, which do not express an EGFR. Blocking Abs against the EGFR or against heparin-binding EGF-like growth factor similarly blocked IL-8-mediated cell migration and in vitro tubulogenesis in HMECs. Furthermore, inhibition of the EGFR also attenuated focus formation in NIH 3T3 expressing the CXCR2. Immunoprecipitations of the EGFR in HMECs and in NIH 3T3 cells expressing the CXCR2 confirmed that the EGFR was phosphorylated following stimulation with IL-8. However, in contrast to previous reports, e.g., for the thrombin receptor, inhibition of matrix metalloproteases blocked IL-8-mediated cell migration only partially, whereas it was ablated by inhibition of cathepsin B. These results indicate that IL-8-induced transactivation of the EGFR is mediated by the CXCR2 and involves cathepsin B, and that this pathway is important for the migratory and tumorigenic effects of IL-8.
This article has been cited by other articles:
|
|
 |
|
  M. L. Petreaca, M. Yao, Y. Liu, K. DeFea, and M. Martins-Green Transactivation of Vascular Endothelial Growth Factor Receptor-2 by Interleukin-8 (IL-8/CXCL8) Is Required for IL-8/CXCL8-induced Endothelial Permeability Mol. Biol. Cell, December 1, 2007; 18(12): 5014 - 5023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Brat, A. C. Bellail, and E. G. Van Meir The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis Neuro-oncol, April 1, 2005; 7(2): 122 - 133. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Lefranc, T. Mijatovic, V. Mathieu, S. Rorive, C. Decaestecker, O. Debeir, J. Brotchi, P. Van Ham, I. Salmon, and R. Kiss Characterization of Gastrin-Induced Proangiogenic Effects In vivo in Orthotopic U373 Experimental Human Glioblastomas and In vitro in Human Umbilical Vein Endothelial Cells Clin. Cancer Res., December 15, 2004; 10(24): 8250 - 8265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhao, A. Wimmer, K. Trieu, R. G. DiScipio, and I. U. Schraufstatter Arrestin Regulates MAPK Activation and Prevents NADPH Oxidase-dependent Death of Cells Expressing CXCR2 J. Biol. Chem., November 19, 2004; 279(47): 49259 - 49267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Carp Cytokines in recurrent miscarriage Lupus, September 1, 2004; 13(9): 630 - 634. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
