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2015 ; 6
(7
): 4633-48
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The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of
virus-independent, FGF2-driven tumors
#MMPMID25609197
Liekens S
; Noppen S
; Gijsbers S
; Sienaert R
; Ronca R
; Tobia C
; Presta M
Oncotarget
2015[Mar]; 6
(7
): 4633-48
PMID25609197
show ga
The FDA-approved anti-DNA virus agent cidofovir (CDV) is being evaluated in phase
II/III clinical trials for the treatment of human papillomavirus (HPV)-associated
tumors. However, previous observations had shown that CDV also inhibits the
growth of vascular tumors induced by fibroblast growth factor-2
(FGF2)-transformed FGF2-T-MAE cells. Here, we demonstrate that CDV inhibits
metastasis induced by FGF2-driven, virus-independent tumor cells. Pre-treatment
of luciferase-expressing FGF2-T-MAE cells with CDV reduced single cell survival
and anchorage-independent growth in vitro and lung metastasis formation upon
intravenous inoculation into SCID mice. This occurred in the absence of any
effect on homing of FGF2-T-MAE cells to the lungs and on the growth of
subconfluent cell cultures or subcutaneous tumors in mice. Accordingly, CDV
protected against lung metastasis when given systemically after tumor cell
injection. Lung metastases in CDV-treated mice showed reduced Ki67 expression and
increased nuclear accumulation of p53, indicating that CDV inhibits metastasis by
affecting single cell survival properties. The anti-metastatic potential of CDV
was confirmed on B16-F10 melanoma cells, both in zebrafish embryos and mice.
These findings suggest that CDV may have therapeutic potential as an
anti-metastatic agent and warrants further study to select those tumor types that
are most likely to benefit from CDV therapy.