Universität zu Köln

Koch, Konrad R., Refaian, Nasrin, Hos, Deniz, Schlereth, Simona L., Bosch, Jacobus J., Cursiefen, Claus and Heindl, Ludwig M. (2014). Autocrine Impact of VEGF-A on Uveal Melanoma Cells. Invest. Ophthalmol. Vis. Sci., 55 (4). S. 2697 - 2705. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. 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). METHODS. 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). RESULTS. 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. CONCLUSIONS. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koch, Konrad R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Refaian, Nasrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hos, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlereth, Simona L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bosch, Jacobus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindl, Ludwig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-441182
DOI:	10.1167/iovs.13-13254
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	55
Number:	4
Page Range:	S. 2697 - 2705
Date:	2014
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL-GROWTH-FACTOR; THERAPEUTIC IMPLICATIONS; TUMOR ANGIOGENESIS; INTRAOCULAR TUMORS; FACTOR RECEPTOR-2; OCULAR MELANOMA; TYROSINE KINASE; BLADDER-CANCER; IN-VITRO; BEVACIZUMAB Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44118