FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer.
Fibroblast growth factor 8 (FGF-8) is expressed at an increased level in a high proportion of prostate cancers and it is associated with a poor prognosis of the disease. Our aim was to study the effects of FGF-8b on proliferation of PC-3 prostate cancer cells and growth of PC-3 tumors, and to identify FGF-8b-associated molecular targets. Expression of ectopic FGF-8b in PC-3 cells caused a 1.5-fold increase in cell proliferation in vitro and a four- to fivefold increase in the size of subcutaneous and orthotopic prostate tumors in nude mice. Tumors expressing FGF-8b showed a characteristic morphology with a very rich network of capillaries. This was associated with increased spread of the cancer cells to the lungs as measured by RT-qPCR of FGF-8b mRNA. Microarray analyses revealed significantly altered, up- and downregulated, genes in PC-3 cell cultures (169 genes) and in orthotopic PC-3 tumors (61 genes). IPA network analysis of the upregulated genes showed the strongest association with development, cell proliferation (CRIP1, SHC1), angiogenesis (CCL2, DDAH2), bone metastasis (SPP1), cell-to-cell signaling and energy production, and the downregulated genes associated with differentiation (DKK-1, VDR) and cell death (CYCS). The changes in gene expression were confirmed by RT-qPCR. In conclusion, our results demonstrate that FGF-8b increases the growth and angiogenesis of orthotopic prostate tumors. The associated gene expression signature suggests potential mediators for FGF-8b actions on prostate cancer progression and metastasis.
Valta
Maija P
MP
Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Finland. maija.valta@utu.fi
Tuomela
Johanna
J
Vuorikoski
Heikki
H
Loponen
Niina
N
Väänänen
Riina-Minna
RM
Pettersson
Kim
K
Väänänen
H Kalervo
HK
Härkönen
Pirkko L
PL
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051524:Fibroblast Growth Factor 8 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology
C496456:FGF8 protein, human; D051524:Fibroblast Growth Factor 8