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

In English

Författare

  • Maija P. Valta
  • Johanna Tuomela
  • Heikki Vuorikoski
  • Niina Loponen
  • Riina-Minna Vaananen
  • Kim Pettersson
  • H. Kalervo Vaananen
  • Pirkko Härkönen

Summary, in English

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.

Publiceringsår

2009

Språk

Engelska

Sidor

769-784

Publikation/Tidskrift/Serie

Journal of Cellular Biochemistry

Volym

107

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Cancer and Oncology

Nyckelord

  • MICROARRAY
  • GENE EXPRESSION
  • ANGIOGENESIS
  • FGF-8
  • ORTHOTOPIC PROSTATE
  • TUMORS
  • PROSTATE CANCER

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0730-2312