Autocrine impact of VEGF-A on uveal melanoma cells
Koch KR, Refaian N, Hos D, Schlereth SL, Bosch JJ, Cursiefen C, Heindl LM (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Book Volume: 55
Pages Range: 2697-704
Journal Issue: 4
Abstract
Tumor-derived VEGF-A, apart from expediting sufficient vascularization, subsequent tumor growth, and metastatic spread, can act on malignant cells themselves provided that VEGF receptors 1 or 2 (VEGF-R1, -R2) are co-expressed. The study goal was to investigate whether such autocrine VEGF-A signaling exists in uveal melanoma (UM).Primary (MEL-270, OM-431) and metastatic (OMM-2.3, OMM-2.5) UM cell lines were analyzed for VEGF-A, VEGF-R1, and VEGF-R2 expression by RT-PCR, ELISA (VEGF-A protein), and immunocytochemistry (VEGF receptors). Proliferation of UM cells incubated with neutralizing anti-VEGF-A antibody bevacizumab (<= 2.5 mg/mL), or VEGF-A (<= 100 ng/mL) was assessed by bromodeoxyuridine (BrdU) ELISA. It was measured by real-time PCR, whether VEGF-A (100 ng/mL) modulated the expression ratio of VEGF-A itself and its antiangiogenic antagonist pigment epithelium-derived factor (PEDF).All UM cells expressed VEGF-A, VEGF-R1, VEGF-R2 mRNA, and protein. In each cell line, the proliferation was stimulated by VEGF-A or inhibited by blocking VEGF-A, or both: bevacizumab significantly decreased the proliferation in MEL-270 (P = 0.005), OMM-2.3 (P = 0.001), and OMM-2.5 (P = 0.011). Increased VEGF-A signaling significantly raised the proliferation in MEL-270, OM-431 (P < 0.001, respectively), and OMM-2.3 (P = 0.043) in a dose-dependent manner but did not significantly change the VEGF-A/PEDF mRNA expression ratio.Autocrine VEGF-A signaling seems to be present in UM, sustaining the proliferation of both primary and metastatic UM cells. Apparently, VEGF-A signaling in UM cells neither acts retroactively on VEGF-A expression, in the sense of a feedback loop, nor contributes to a pro-angiogenic shift of the VEGF-A/PEDF ratio.
Involved external institutions
Germany (DE)How to cite
APA:
Koch, K.R., Refaian, N., Hos, D., Schlereth, S.L., Bosch, J.J., Cursiefen, C., & Heindl, L.M. (2014). Autocrine impact of VEGF-A on uveal melanoma cells. Investigative Ophthalmology & Visual Science, 55(4), 2697-704. https://doi.org/10.1167/iovs.13-13254
MLA:
Koch, Konrad R., et al. "Autocrine impact of VEGF-A on uveal melanoma cells." Investigative Ophthalmology & Visual Science 55.4 (2014): 2697-704.
BibTeX: Download