CLINICAL SCIENCE

Uveal melanomas express vascular endothelial growth factor and basic fibroblast growth factor and support endothelial cell growth

S R Boyd^1,2, D S W Tan¹, L de Souza¹, M H Neale¹, N E Myatt¹, R A Alexander¹, M Robb⁴, J L Hungerford³ and I A Cree⁵

¹ Department of Pathology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK
² Department of Ophthalmology, and the Vascular Biology Research Group, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Canada M5B 1W8
³ Moorfields Eye Hospital, City Road, London EC1V 2PD, UK
⁴ Vascular Biology Research Group, Terence Donnelly Centre for Cardiovascular Research, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Canada M5B 1W8
⁵ Translational Oncology Research Centre, Department of Histopathology, Michael Darmady Laboratory, Queen Alexandra Hospital, Cosham, Portsmouth PO6 3LY, UK

Correspondence to:
Correspondence to:
Professor I A Cree, Translational Oncology Research Centre, Department of Histopathology, Michael Darmady Laboratory, Queen Alexandra Hospital, Cosham, Portsmouth PO6 3LY, UK;
ian.cree{at}port.ac.uk

Background: Tumour microvascularity is a significant determinant of prognosis for a large number of different tumours, including uveal melanoma. The development of blood vessels within these and other tumours is partly controlled by soluble pro-angiogenic cytokines, of which basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF) are the best described.

Methods: Because VEGF has been inconsistently found within uveal melanomas and bFGF is described as an autocrine growth factor in cutaneous melanoma, the authors looked at the expression of these cytokines in uveal melanomas using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). The cross talk between uveal melanoma cells and endothelial cells was then assessed in an in vitro co-culture model.

Results: While most tumour cells expressed bFGF at the protein level by immunohistochemistry (89%), relatively few (22%) expressed VEGF, and this was of limited extent. All 20 tumours tested by RT-PCR contained mRNA for both bFGF and VEGF. Co-culture experiments using an ATP based bioassay showed that uveal melanomas could support the growth of a rat brain endothelial cell line (GPNT) and human umbilical vein endothelial cells (HUVEC), and that this could be modulated by cytokines and anti-cytokine antibodies.

Conclusion: These results suggest that angiogenesis within uveal melanoma may be the result of a complex interplay between endothelial and tumour cells, and that bFGF and VEGF could play a part.

Keywords: melanoma; eye; choroid; vascular endothelial growth factor; basic fibroblast growth factor; angiogenesis

Abbreviations: bFGF, basic fibroblast growth factor; BBE, bovine brain extract; BSA, bovine serum albumin; ELISA, enzyme linked immunosorbent assay; HUVEC, human umbilical vein endothelial cells; PCR, polymerase chain reaction; RLU, relative light units; RT-PCR, reverse transcriptase polymerase chain reaction; TBS, TRIS buffered saline; VEGF, vascular endothelial growth factor

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