Platelet factor-4 (PF-4) is an ELR-negative chemokine that exhibits antiangiogenesis
properties. PF-4 inhibits endothelial cell proliferation and migration, angiogenesis
in vitro and in vivo, and tumor growth. However, tumor cells are not directly inhibited
by PF-4. To date, a cell surface receptor that would explain the biological effects
mediated by PF-4 has not been identified. PF-4 is able to interact directly with angiogenesis
growth factors such as fibroblast growth factors (FGFs) and vascular endothelial growth
factors and inhibits their interaction with cell surface receptors. Furthermore, dimerization
of fibroblast growth factors is abrogated by PF-4. Whether PF-4 plays a role as an
endogenous angiogenesis regulator is at present not clear. Several PF-4 fragments
and modified molecules have been made that exhibit antiangiogenesis properties. Among
these is a C-terminal fragment that has a defined structure, retains all the antiangiogenesis
properties of the parent molecule, inhibits growth factor receptor binding, associates
with FGFs, and destabilizes their three-dimensional structure. The relevance of these
observations for the treatment of malignant disease is discussed.
KEYWORDS
Platelet factor-4 - angiogenesis - cancer
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Andreas BikfalviM.D. Ph.D.
Molecular Angiogenesis Laboratory, (INSERM E0113), Université Bordeaux I
Avenue des Facultés
33 405 Talence, France
Email: a.bikfalvi@angio.u-bordeaux.fr