Premium
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
Author(s) -
Vandercappellen Jo,
Noppen Samuel,
Verbeke Hannelien,
Put Willy,
Conings René,
Gouwy Mieke,
Schutyser Evemie,
Proost Paul,
Sciot Raf,
Geboes Karel,
Opdenakker Ghislain,
Van Damme Jo,
Struyf Sofie
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0407206
Subject(s) - biology , chemokine , angiogenesis , cancer research , immunology , inflammation , ccl7 , chemotaxis , cytokine , mesenchymal stem cell , cxcl10 , microbiology and biotechnology , biochemistry , receptor
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‐α but inhibited by IFN‐γ, which synergized with IL‐1β to produce the angiostatic CXCL10/IFN‐γ‐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.