science pharmaceutical expo biotech jobs
Originally published online as doi:10.1189/jlb.0407206 on September 7, 2007

Published online before print September 7, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0407206v1
82/6/1519    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vandercappellen, J.
Right arrow Articles by Struyf, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vandercappellen, J.
Right arrow Articles by Struyf, S.
(Journal of Leukocyte Biology. 2007;82:1519-1530.)
© 2007 by Society for Leukocyte Biology

Stimulation of angiostatic platelet factor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells

Jo Vandercappellen*, Samuel Noppen*, Hannelien Verbeke*, Willy Put*, René Conings*, Mieke Gouwy*, Evemie Schutyser*, Paul Proost*, Raf Sciot{dagger}, Karel Geboes{dagger}, Ghislain Opdenakker{ddagger}, Jo Van Damme*,1 and Sofie Struyf*

* Laboratories of Molecular Immunology and
{ddagger} Immunobiology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium; and
{dagger} Department of Pathology, University Hospital Leuven, Leuven, Belgium

1Correspondence: Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: jo.vandamme{at}rega.kuleuven.be

Chemokines affect inflammation and cancer through leukocyte attraction and angiogenesis. Here, we demonstrate that CXCL4L1/platelet factor-4 variant (PF-4var), a highly angiostatic chemokine, is poorly chemotactic for phagocytes and is inducible in monocytes by inflammatory mediators but remained undetectable in macrophages and neutrophils. In addition, CXCL4L1/PF-4var production by mesenchymal tumor cells was evidenced in vitro and in vivo by specific ELISA and immunohistochemistry. CXCL4L1/PF-4var, but not CXCL4/PF-4, was coinduced with the angiogenic chemokine CXCL6/granulocyte chemotactic protein-2 (GCP-2) by cytokines, e.g., IL-1β and IL-17, in sarcoma cells, but not in diploid fibroblasts. Furthermore, the induction of CXCL6/GCP-2 in endothelial cells by IL-1β was enhanced synergistically by TNF-{alpha} but inhibited by IFN-{gamma}, which synergized with IL-1β to produce the angiostatic CXCL10/IFN-{gamma}-induced protein-10. These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. Selective intervention in the chemokine network may drastically disturb this delicate balance of angiogenesis and tissue repair. Application of angiostatic CXCL4L1/PF-4var without attraction of protumoral phagocytes may be beneficial in cancer therapy.

Key Words: angiogenesis • chemokine • cytokine • monocytes