Correlation between the Expression of Angiogenic Factors and Stem Cell Markers in Human Uveal Melanoma
Klára Fodor,
Éva Sipos,
Nikoletta Dobos,
János Nagy,
Zita Steiber,
Gábor Méhes,
Kata Dull,
Lóránt Székvölgyi,
Andrew V. Schally,
Gábor Halmos
Affiliations
Klára Fodor
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary
Éva Sipos
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary
Nikoletta Dobos
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary
János Nagy
Clinical Center, Department of Oncology, University of Debrecen, 4032 Debrecen, Hungary
Zita Steiber
Clinical Center, Department of Ophthalmology, University of Debrecen, 4032 Debrecen, Hungary
Gábor Méhes
Department of Pathology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Kata Dull
Department of Pathology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Lóránt Székvölgyi
MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Andrew V. Schally
Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL 33101, USA
Gábor Halmos
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary
Uveal melanoma (UM) is the most common malignant tumor of the eye with extremely high metastatic potential. UM tumor cells can disseminate only hematogenously, thus, angiogenic signals have a particular role in the prognosis of the disease. Although the presence of cancer stem cells (CSCs) in densely vascularized UMs has been reported previously, their role in the process of hematogenous spread of UM has not been studied. In this study, we investigated the regulation of angiogenesis in UM in correlation with the presence of CSCs. Seventy UM samples were collected to analyze the expression of CSC markers and angiogenic factors. The expression of CSC markers was studied by RT-PCR, Western blotting techniques and IHC-TMA technique. RT-PCR showed high expression of CSC markers, particularly nestin, FZD6 and SOX10 and somewhat lower expression of NGFR. The protein expression of FZD6, HIF-1α and VEGFA was further evaluated in 52 UM samples by the IHC-TMA technique. We report here for the first time a significant correlation between FZD6 and VEGFA expression in UM samples. The observed correlation between FZD6 and VEGFA suggests the presence of CSCs in UM that are associated with the vascularization process.
