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FGF-8b Induces Growth and Rich Vascularization in an Orthotopic PC-3 Model of Prostate Cancer

Valta, Maija P.; Tuomela, Johanna; Vuorikoski, Heikki; Loponen, Niina; Vaananen, Riina-Minna; Pettersson, Kim; Vaananen, H. Kalervo and Härkönen, Pirkko LU (2009) In Journal of Cellular Biochemistry 107(4). p.769-784
Abstract
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... (More)
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. J. Cell. Biochem. 107: 769-784, 2009. (C) 2009 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MICROARRAY, GENE EXPRESSION, ANGIOGENESIS, FGF-8, ORTHOTOPIC PROSTATE, TUMORS, PROSTATE CANCER
in
Journal of Cellular Biochemistry
volume
107
issue
4
pages
769 - 784
publisher
Wiley-Blackwell
external identifiers
  • wos:000267813600023
  • scopus:67650069283
ISSN
0730-2312
DOI
10.1002/jcb.22175
language
English
LU publication?
yes
id
ae329a23-0938-4f80-b7d2-6210fb898b92 (old id 1462508)
date added to LUP
2009-08-31 11:05:26
date last changed
2017-07-30 03:42:13
@article{ae329a23-0938-4f80-b7d2-6210fb898b92,
  abstract     = {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. J. Cell. Biochem. 107: 769-784, 2009. (C) 2009 Wiley-Liss, Inc.},
  author       = {Valta, Maija P. and Tuomela, Johanna and Vuorikoski, Heikki and Loponen, Niina and Vaananen, Riina-Minna and Pettersson, Kim and Vaananen, H. Kalervo and Härkönen, Pirkko},
  issn         = {0730-2312},
  keyword      = {MICROARRAY,GENE EXPRESSION,ANGIOGENESIS,FGF-8,ORTHOTOPIC PROSTATE,TUMORS,PROSTATE CANCER},
  language     = {eng},
  number       = {4},
  pages        = {769--784},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Cellular Biochemistry},
  title        = {FGF-8b Induces Growth and Rich Vascularization in an Orthotopic PC-3 Model of Prostate Cancer},
  url          = {http://dx.doi.org/10.1002/jcb.22175},
  volume       = {107},
  year         = {2009},
}