Expression and distribution of MUC18 in human uveal melanoma
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The immunoglobulin superfamily protein MUC18 is involved in transendothelial migration and signal transduction, and is expressed in malignancies including cutaneous melanoma. Recent in vitro studies showed evidence of increased MUC18 protein in some uveal melanoma cell lines with an increased potential for invasion. We assessed seven uveal and three metastasis-derived melanoma cell lines for the expression of MUC18 mRNA and protein by RT-PCR, and immunoblotting and immunocytochemistry, respectively. We also examined the expression and distribution of MUC18 in paraffin sections of primary uveal melanomas (n = 23; 5/23 spindle; 18/23 mixed and epithelioid) and normal eyes (n = 3) using a polyclonal goat anti-human antibody to MUC18 visualized with peroxidase and Vector NovaRED. Distribution and intensity of immunostaining was graded semi-quantitatively (grade 0 to 3) by 2 independent observers. All cell lines expressed MUC18 mRNA and protein (∼130 kDa), and showed punctate cell membrane MUC18 immunostaining. Primary melanomas displayed heterogeneous cell membrane and cytoplasmic MUC18, with moderate to strong immunolabelling (≥grade 2) in ∼70% of tumours. Vasculature in tumours and in retina and choroid of all melanoma-affected and normal eyes showed intense MUC18 immunostaining. These observations further suggest a role for MUC18 in uveal melanoma growth; moreover, interactions between MUC18-positive melanoma cells and vasculature may be important for the hematogenous spread of cells during metastases.
KeywordsImmunohistochemistry Oncology Uveal melanoma Vascular endothelium
Cell lines were kindly provided as follows: OCM-1, OCM-3 and OCM-8 (Dr J Kan-Mitchell, Karmanos Cancer Institute, Department of Pathology and Immunology, Wayne State University, Detroit); OMM-1 (Dr GP Luyten, Erasmus University, Rotterdam), 92-1 (Dr MJ Jager, Leiden University Medical Center, Leiden); Mel202 (Dr B. Ksander, Schepens Eye Research Institute, Boston) and OCM-1A, C918, MUM2B and MUM2C (Dr MJ Hendrix, Children’s Memorial Research Center, Northwestern University, Chicago).
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