Tuomela et al. BMC Cancer 2010, 10:596 http://www.biomedcentral.com/1471-2407/10/596 R E S E A R C H A R T I C L E Open Access Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts Johanna Tuomela1,2*, Tove J Grönroos3, Maija P Valta1, Jouko Sandholm4, Aleksi Schrey5, Jani Seppänen1,2, Päivi Marjamäki3, Sarita Forsback6, Ilpo Kinnunen5, Olof Solin7, Heikki Minn8, Pirkko L Härkönen1,9 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. Background Hypoxia is a common feature of prostate tumours [1]. A low oxygen concentration is known to make tumour cells resistant to radiation therapy and chemotherapy [2]. Furthermore, there is evidence that hypoxia may lead to increasingly malignant behaviour of tumour cells [3,4]. Hypoxia leads to disruption of microenvir- onmental homeostasis in tumours, where metabolic changes, involving diffusion gradients of oxygen and glucose, develop at microregional level [5]. A common * Correspondence: jomitu@utu.fi 1Institute of Biomedicine, Department of Cell Biology and Anatomy, University of Turku, Turku, Finland Full list of author information is available at the end of the article feature of invasive cancers is altered glucose metabo- lism, including both aerobic and anaerobic glycolysis [6]. Conversion of glucose to lactic acid in the pre- sence of oxygen is known as aerobic glycolysis or the “Warburg effect”. The molecular mechanisms leading to upregulated glycolysis in tumours are not well known, but increased glucose uptake and elevated expression of glucose transporters (GLUTs), such as GLUT1, are commonly seen in tumour cells [7]. In prostate cancer, the expression of GLUT1 is also cor- related with Gleason score [8]. Members of the GLUT gene family are known to be regulated by hypoxia- inducible transcription factor 1 (HIF1), which is strongly upregulated under hypoxic conditions [9]. © 2010 Tuomela et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.