Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Johanna Tuomela, Tove J Grönroos, Maija P Valta, Jouko Sandholm, Aleksi Schrey, Jani Seppänen, Päivi Marjamäki, Sarita Forsback, Ilpo Kinnunen, Olof Solin, Heikki Minn, Pirkko L Härkönen

ABSTRACT

BACKGROUND: Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. METHODS: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([18F]FDG) and hypoxia ([18F]EF5), and intratumoral polarographic measurements of pO2. RESULTS: Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO2 measurements, [18F]EF5 and [18F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. CONCLUSION: FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts. More... »

PAGES

596

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2407-10-596

DOI

http://dx.doi.org/10.1186/1471-2407-10-596

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044857053

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21034500


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