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26.08.2016 | Research Paper | Ausgabe 8/2016

Clinical & Experimental Metastasis 8/2016

Expression of natural killer cell regulatory microRNA by uveal melanoma cancer stem cells

Zeitschrift:
Clinical & Experimental Metastasis > Ausgabe 8/2016
Autoren:
Powrnima Joshi, Mitra Kooshki, Wayne Aldrich, Daniel Varghai, Maciej Zborowski, Arun D. Singh, Pierre L. Triozzi
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10585-016-9815-9) contains supplementary material, which is available to authorized users.

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.

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