Angiogenic profile of uveal melanoma.
Uveal melanoma develops in one of the most capillary-rich tissues of the body and is disseminated hematogenously. Knowledge of the nature and the spatiotemporal expression of angiogenic factors in uveal melanoma is essential to the development of new treatment strategies, especially with regard to improving survival. In this study, we measured the angiogenic potential of several angiogenic factors in different uveal melanoma cell lines, in an in vivo model, and in primary tumor material from patients with melanoma. Most uveal melanoma cell lines expressed vascular endothelial growth factor (VEGF)-A (isoforms 121, 165, 189), VEGF-B, VEGF-C, VEGF-D, and basic fibroblastic growth factor (b-FGF) to various extents. The expression of VEGF-A 121 was always higher than that of the other VEGF-A isoforms, suggesting that VEGF-A 121 is the most abundant VEGF-A isoform. All experimentally induced tumors expressed VEGF-A, VEGF-B, VEGF-C, VEGF-D, and basic fibroblastic growth factor (b-FGF). Similarly, significant amounts of mRNA for VEGF-B, VEGF-C, VEGF-D, and b-FGF were detected in uveal melanoma material from patients. In contrast, VEGF-A mRNA (121, 165, 189) was low (9/28) or not detectable in the tumor samples. The synthesis of VEGF-A 165 and b-FGF protein by various cell lines was measured by enzyme-linked immunosorbent assay (ELISA). Most uveal melanoma cell lines, but not normal melanocytes, strongly synthesized and secreted VEGF-A 165 and b-FGF during cell culture. Our data suggest that the expression of (lymph) angiogenic factors may play a causal role in the angiogenesis and progression of uveal melanoma and distant metastasis.
Notting
Irene Christa
IC
Department of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands. i.c.notting@lumc.nl
Missotten
Guy Sam Omer Antoon
GS
Sijmons
Bianca
B
Boonman
Zita Francisca Helena Maria
ZF
Keunen
Jan Ernest Everard
JE
van der Pluijm
Gabriel
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000869:Anterior Eye Segment / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics; D020033:Protein Isoforms; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000235:genetics*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*
D020033:Protein Isoforms; D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D012313:RNA