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


CONCLUSIONS
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.
Boyd
S R
SR
Department of Pathology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK.
Tan
D S W
DS
de Souza
L
L
Neale
M H
MH
Myatt
N E
NE
Alexander
R A
RA
Robb
M
M
Hungerford
J L
JL
Cree
I A
IA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000379:methods; D002830:Choroid Neoplasms / Q000098:blood supply / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015811:Iris Neoplasms / Q000098:blood supply / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism*; D008833:Microcirculation; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000098:blood supply / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000255:Adenosine Triphosphate