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Ariela Lifshits Miller, Amnon Peled, Jacob Pe'er, Shahar Frenkel; CXCR4 Expression In Primary And Metastatic Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1453.
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The purpose of this study was to determine the expression of the CXCR4 chemokine receptor in primary and metastatic Uveal Melanoma (UM) tissues and in a UM cell line.
Immunohistochemistry to detect CXCR4 (monoclonal anti-human CXCR4, R&D systems, Minneapolis, USA) was performed on 17 eyes of 17 patients with UM, as well as on 9 liver sections of 9 metastatic UM patients. The tissues were analyzed and graded according to the intensity of the stain from 0-4 (0- being no staining, and 4- very intense staining). The primary tumors were examined for tumor cell type, vasculogenic mimicry patterns, mitotic figures, and tumor size (largest basal diameter and tumor height). mRNA from the OCM1 cell line was examined for the expression of CXCR4 and VEGF before and after stimulation with SDF1 (CXCL12), as well as expression of SDF1 mRNA.
CXCR4 expression was observed in both primary and metastatic uveal melanoma. In the 17 primary tumors 10 (59%) tumors stained grade 3. The mean staining intensity was 2.59. In the metastatic tumor 3/9 (33.3%) liver sections stained grade 4. The mean staining intensity was 2.56. No correlation was found between CXCR4 staining intensity and any of the histopathologic parameters. SDF1 mRNA was not detected in OCM1 cells. mRNA levels for CXCR4 did not increase after stimulation with SDF1, but this stimulation increased the mRNA levels of VEGF after 24 and 48 hours.
CXCR4 was found to be expressed in both the primary and the metastatic tumors. mRNA levels of CXCR4 did not increase after stimulation with external SDF1. However, VEGF mRNA levels increased after SDF1 stimulation. An inhibiting agent for CXCR4 protein is presently available and may be a new direction of treatment for both primary and metastatic uveal melanoma. However, this pathway needs further investigation.
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