ABSTRACT
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.
