HERV-K activation is strictly required to sustain CD133+ melanoma cells with stemness features

Background: melanoma is a heterogeneous tumor in which phenotype-switching and cd133 marker have been associated with metastasis promotion and chemotherapy resistance. cd133 positive (cd133+) subpopulation has also been suggested as putative cancer stem cell (csc) of melanoma tumor. human endogenous retrovirus type k (herv-k) has been described to be aberrantly activated during melanoma progression and implicated in the etiopathogenesis of disease. earlier,we reported that stress-induced herv-k activation promotes cell malignant transformation and reduces the immunogenicity of melanoma cells. herein,we investigated the correlation between herv-k and the cd133+ melanoma cells during microenvironmental modifications. methods: tvm-a12 cell line,isolated in our laboratory from a primary human melanoma lesion,and other commercial melanoma cell lines (g-361,wm-115,wm-266-4 and a375) were grown and maintained in the standard and stem cell media. rna interference,real-time pcr,flow cytometry analysis,self-renewal and migration/invasion assays were performed to characterize cell behavior and herv-k expression. results: melanoma cells,exposed to stem cell media,undergo phenotype-switching and expansion of cd133+ melanoma cells,concomitantly promoted by herv-k activation. notably,the sorted cd133+ subpopulation showed stemness features,characterized by higher self-renewal ability,embryonic genes expression,migration and invasion capacities compared to the parental cell line. rna interference-mediated downregulation experiments showed that herv-k has a decisive role to expand and maintain the cd133+ melanoma subpopulation during microenvironmental modifications. similarly,non nucleoside reverse transcriptase inhibitors (nnrtis) efavirenz and nevirapine were effective to restrain the activation of herv-k in melanoma cells,to antagonize cd133+ subpopulation expansion and to induce selective high level apoptosis in cd133+ cells. conclusions: herv-k activation promotes melanoma cells phenotype-switching and is strictly required to expand and maintain the cd133+ melanoma cells with stemness features in response to microenvironmental modifications. © 2017 the author(s).