Polysulfated heparinoids selectively inactivate heparin-binding
angiogenesis factors.



Zugmaier G, Favoni R, Jaeger R, Rosen N, Knabbe C.



Department of Hematology/Oncology, Philipps-University, Marburg,
Germany.



Angiogenesis is a prerequisite for tumor expansion and metastasis.
The angiogenic potential of the heparin-binding growth factors
acidic fibroblast growth factor (FGF) and basic FGF has been
demonstrated in various publications. We studied the inhibitory
effects of suramin and the polysulfated heparinoids pentosan
polysulfate, dextran sulfate, and fucoidan on the action of FGF. As
an experimental model, we used the adrenal cancer cell line SW 13,
whose anchorage-independent growth depends on the presence of FGF.
The polysulfated heparinoids inhibited FGF-induced growth and
binding to the receptor at an IC50 of 0.5-3 micrograms/ml. Suramin
inhibited FGF at an IC50 of 100 micrograms/ml. The polysulfated
heparinoids exerted no effect on IGF-1 or TGF alpha-related growth.
Suramin inhibited the anchorage-independent growth induced by IGF-1
or TGF alpha only at an IC50 of 100 micrograms/ml. Our results
indicate that suramin inhibits growth factors in a nonselective way.
By contrast, polysulfated heparinoids exert a selective inhibitory
effect on heparin binding angiogenesis factors at an IC50, which is
100 times below the IC50 of suramin. Therefore, the administration
of polysulfated heparinoids might become a novel approach to tumor
therapy based on blocking angiogenesis.



PMID: 10667230 [PubMed - indexed for MEDLINE]