FGF-8b Induces Growth and Rich Vascularization in an Orthotopic PC-3 Model of Prostate Cancer
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1462508
- author
- Valta, Maija P. ; Tuomela, Johanna ; Vuorikoski, Heikki ; Loponen, Niina ; Vaananen, Riina-Minna ; Pettersson, Kim ; Vaananen, H. Kalervo and Härkönen, Pirkko LU
- organization
- publishing date
- 2009
- 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
- pmid:19415685
- ISSN
- 0730-2312
- DOI
- 10.1002/jcb.22175
- language
- English
- LU publication?
- yes
- additional info
- Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:27.
- id
- ae329a23-0938-4f80-b7d2-6210fb898b92 (old id 1462508)
- date added to LUP
- 2016-04-01 12:04:35
- date last changed
- 2022-01-26 22:29:33
@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}}, keywords = {{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}}, doi = {{10.1002/jcb.22175}}, volume = {{107}}, year = {{2009}}, }