title: Expression of natural killer cell regulatory microRNA by uveal melanoma cancer stem cells.
abstract: Natural killer (NK) cells are implicated in the control of metastasis in uveal melanoma, a process that has been ascribed to its cancer stem cell subpopulation. NK cell activation is regulated by specific microRNA (miR). The NK cell sensitivity and regulatory miR production of uveal melanoma cancer stem cells was examined. Cancer stem cells enriched from aggressively metastatic MUM2B uveal melanoma cells by selecting CD271+cells or propagating as non-adherent spheres in stem-cell supportive were more resistant to NK cell cytolysis than cancer stem cells enriched from less aggressively metastatic OCM1 uveal melanoma cells. Both MUM2B and OCM1 cells expressed and secreted NK cell regulatory miRs, including miR 146a, 181a, 20a, and 223. MUM2B cells expressed and secreted miR-155; OCM1 cells did not. Transfecting MUM2B cells with anti-miR-155 increased NK cell sensitivity. CD271+cells were identified in the blood of patients with metastatic uveal melanoma and were characterized by low expression of melanocyte differentiation determinants and by the ability to form non-adherent spheres in stem-cell supportive media. These cells also expressed NK cell regulatory miRs, including miR-155. These results indicate that uveal melanoma cancer stem cells can vary in their sensitivity to NK cell lysis and their expression of NK cell regulatory miRs. Circulating CD271+cells from patients with metastatic uveal melanoma manifest cancer stem cell features and express miRs associated with NK cell suppression, including miR-155, that may contribute to metastatic progression.
authors: Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Powrnima
authors: P
authors: Joshi
authors: Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC, 27157, USA.
authors: Mitra
authors: M
authors: Kooshki
authors: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Wayne
authors: W
authors: Aldrich
authors: Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Daniel
authors: D
authors: Varghai
authors: Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Maciej
authors: M
authors: Zborowski
authors: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Arun D
authors: AD
authors: Singh
authors: Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC, 27157, USA. ptriozzi@wakehealth.edu.|Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA. ptriozzi@wakehealth.edu.
authors: Pierre L
authors: 0000-0003-2488-6136
authors: PL
authors: Triozzi
mesh_terms: D000068816:Adapalene / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology*; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D000068816:Adapalene
keywords: CD271; MHC class I-related chain A; Major histocompatibility complex class I molecules; Melanospheres; Microphthalmia-associated transcription factor; miR-155