Inhibition of angiogenic activity of renal carcinoma by an antisense oligonucleotide targeting fibroblast growth factor-2.
BACKGROUND
Fibroblast growth factor-2 (FGF-2) induces angiogenesis, critical for the growth and metastatic spread of tumors.


METHODS
The effect of blocking FGF-2 synthesis by an antisense phosphorothioate oligodeoxynucleotide (PS-ODN2) was evaluated on the angiogenic activity of Caki-1 and of a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990). After the transfection with PS-ODN2, FGF-2 mRNA, protein expression and angiogenic activity were evaluated.


RESULTS
In Caki-1, a not significant decrease in the released FGF-2 was observed after 72 hours. In CRBM-1990, a not significant decrease in intracellular FGF-2 protein was observed after 72 hours. Endothelial cell migration induced by the conditioned media from Caki-1 treated with PS-ODN2 for 72 hours was significantly reduced.


CONCLUSIONS
PS-ODN2 treatment of the established line Caki-1 induced minimal variations in FGF-2 expression, but inhibited endothelial cell migration. In CRBM-1990 cells, PS-ODN2 determined a decrease in intracellular protein without reducing the ability to induce endothelial cell migration and proliferation.
Cenni
Elisabetta
E
Laboratory for Pathophysiology of Orthopedic Implants, Istituti Ortopedici Rizzoli, Bologna, Italy. elisabetta.cenni@ior.it
Perut
Francesca
F
Zuntini
Monia
M
Granchi
Donatella
D
Amato
Ilaria
I
Avnet
Sofia
S
Brandi
Maria Luisa
ML
Giunti
Armando
A
Baldini
Nicola
N
D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2