Increased expression of fibroblast growth factors (FGFs) and their receptor by protamine and suramin on Kaposi's sarcoma-derived cells.
Growth factors, such as bFGF, have been shown to exert autocrine and paracrine effects on the growth of Kaposi's Sarcoma (KS)-derived cells, which suggested that the inhibitors of angiogenesis may be promising for KS treatment. However, KS lesions have been found to continue to enlarge after patients had been treated with FGF binding antagonists such as suramin. We investigated the effect of protamine and suramine on the growth of KS derived cells in vitro. Although both of these agents which are FGF binding antagonists were found to inhibit the incorporation of 3H thymidine in KS-derived cultured cells, increased expression of bFGF, FGF5 and the FGF receptor was observed after the KS cells were exposed to these substances. These results might explain the clinical observation that FGF binding antagonists such as suramin caused an apparent stimulation of KS tumor growth when administered systemically to patients with AIDS-related KS.
Huang
Y Q
YQ
Department of Microbiology, New York University Medical Center, NY 10016.
Li
J J
JJ
Nicolaides
A
A
Zhang
W G
WG
Friedman-Kien
A E
AE
D001483:Base Sequence; D015139:Blotting, Southern; D003574:Cytochrome c Group / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011479:Protamines / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000302:isolation & purification; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000187:drug effects; D012514:Sarcoma, Kaposi / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003574:Cytochrome c Group; C496449:FGF5 protein, human; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D011479:Protamines; D012334:RNA, Neoplasm; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D051521:Fibroblast Growth Factor 5; D013498:Suramin; D005346:Fibroblast Growth Factors