Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines.
Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angiogenic and immunosuppressive factors in seven human uveal melanoma cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR): secreted interleukin-1 receptor antagonist (sIL-1ra), interleukin (IL)-6, IL-8, IL-10, transforming growth factor (TGF)-alpha, TGFbeta, vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), angiopoietin-1 and angiopoietin-2. In addition, the secretion of sIL-1ra, IL-6, IL-8, IL-10, TGFbeta and VEGF was assayed by enzyme linked immunosorbent assay (ELISA). The potential of uveal melanoma cell lines to convert plasminogen to angiostatin was tested in an in vitro assay. All the factors except angiopoietin-1 were determined in one or more cell lines using RT-PCR, although these results were not necessarily confirmed by ELISA. Expression of VEGF and angiopoietin-2 was found in all seven cell lines. Production of angiostatin was observed in one cell line. All seven cell lines examined expressed angiogenic factors and most cell lines expressed immunosuppressive factors. The expression of VEGF and angiopoietin-2 in combination with a lack of angiopoietin-1 expression suggest high vascular remodelling capacity and could be of great relevance for the metastatic potential of uveal melanoma.
Ijland
S A
SA
Department of Ophthalmology, Leiden University Medical Center, The Netherlands. steven.ijland@usa.net
Jager
M J
MJ
Heijdra
B M
BM
Westphal
J R
JR
Peek
R
R
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D043168:Angiostatins; D017077:Culture Media, Conditioned / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis; D010958:Plasminogen / Q000096:biosynthesis / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000098:blood supply / Q000378:metabolism*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D017077:Culture Media, Conditioned; D006133:Growth Substances; C507763:IL1RN protein, human; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D016753:Interleukin-10; D015291:Transforming Growth Factors; D043168:Angiostatins; D010958:Plasminogen