ABCB5 Maintains Melanoma-Initiating Cells through a Proinflammatory Cytokine Signaling Circuit

Wilson, B. J.; Saab, Karim R.; Ma, Jie; Schatton, Tobias; Pütz, Pablo; Zhan, Qimin; Murphy, Gëorge F.; Gasser, Martin; Waaga-Gasser, Ana Maria; Frank, Natasha Y.; Frank, Markus H.

doi:10.1158/0008-5472.can-14-0582

Cited by 122 publications

(125 citation statements)

References 50 publications

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“…Currently, the mechanism of this event is unknown. Very recently Wilson et al [59] have reported that melanoma SC maintenance is dependent on ABCB5-dependent secretion of Il1β another inflammatory cytokine. Is TNF-induced ABCB5 part of this regulatory circuit?…”

Section: Discussionmentioning

confidence: 99%

Transient TNF regulates the self-renewing capacity of stem-like label-retaining cells in sphere and skin equivalent models of melanoma

Ostyn

Machhour

Bégard

et al. 2014

Cell Communication and Signaling

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Background: It is well established that inflammation promotes cancer, including melanoma, although the exact mechanisms involved are less known. In this study, we tested the hypothesis that inflammatory factors affect the cancer stem cell (CSC) compartment responsible for tumor development and relapse. Results: Using an inducible histone 2B-GFP fusion protein as a tracer of cell divisional history, we determined that tumor necrosis factor (TNF), which is a classical pro-inflammatory cytokine, enlarged the CSC pool of GFP-positive label-retaining cells (LRCs) in tumor-like melanospheres. Although these cells acquired melanoma stem cell markers, including ABCB5 and CD271, and self-renewal ability, they lost their capacity to differentiate, as evidenced by the diminished MelanA expression in melanosphere cells and the loss of pigmentation in a skin equivalent model of human melanoma. The undifferentiated cell phenotype could be reversed by LY294002, which is an inhibitor of the PI3K/AKT signaling pathway, and this reversal was accompanied by a significant reduction in CSC phenotypic markers and functional properties. Importantly, the changes induced by a transient exposure to TNF were long-lasting and observed for many generations after TNF withdrawal.

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Section: Discussionmentioning

confidence: 99%

Transient TNF regulates the self-renewing capacity of stem-like label-retaining cells in sphere and skin equivalent models of melanoma

Ostyn

Machhour

Bégard

et al. 2014

Cell Communication and Signaling

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“…10 Thus, our results support the notion that ABCB5 could be considered as biomarker of melanoma stem-like cells. 8,10,25,46,47 Moreover, both the colony-forming capacity (not shown) and frequency of ABCB5-positive cells remained unaffected during transition from melanospheres to cell aggregates. This might indicate that this subpopulation of melanoma cells exhibiting cancer stem cell properties was present in all forms of cultures and was stable during prolonged culturing.…”

Section: Discussionmentioning

confidence: 94%

“…Most recently, reciprocal paracrine interactions between different subpopulations of melanoma has been demonstrated as being involved in CSC maintenance. 47 The mechanisms driving intratumoral variation in cellular function have to be elucidated. 6 As MITF can be expressed at different levels in distinct subpopulations of the heterogeneous tumor mass, 69 it would be interesting to elucidate how a MITF-enriched subpopulation can interplay with other subpopulations present in heterogeneous melanoma to support the growth and maintenance of the tumor, and whether this networking function is clinically relevant.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic diversity of patient-derived melanoma populations in stem cell medium

Sztiller-Sikorska

Hartman

Talar

et al. 2015

Laboratory Investigation

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Melanomas are highly heterogeneous tumors and there is no treatment effective at achieving long-term remission for metastatic melanoma patients. Thus, an appropriate model system for studying melanoma biology and response to drugs is necessary. It has been shown that composition of the medium is a critical factor in preserving the complexity of the tumor in in vitro settings, and melanospheres maintained in stem cell medium are a good model in this respect. In the present study, we observed that not all nodular melanoma patient-derived cell populations grown in stem cell medium were capable of forming melanospheres, and cell aggregates and anchorage-independent single-cell cultures emerged instead. Self-renewing capacity and unlimited growth potential indicated the presence of cells with stem-like properties in all patient-derived populations but immunophenotype and MITF expression exhibited variability. Enhanced MITF expression and activity was observed in melanospheres in comparison with cell aggregates and single-cell culture, and hypoxic-like conditions that increased the ability of single-cell population to form melanospheres enhanced MITF expression and cell pigmentation as well. Thus, MITF seems to be a critical transcription factor for formation of both patient-derived and hypoxia-induced melanospheres. After 2 years of continuous culturing, melanospheres progressively underwent transition into cell aggregates that was accompanied by changes in expression of several MITF-dependent genes associated with melanogenesis and survival and alterations in the composition of subpopulations but not in the frequency of ABCB5-positive cells. Several biological properties of parent tumor are well preserved in patient-derived melanospheres, but during prolonged culturing the heterogeneity is substantially lost when the melanospheres are substituted by cell aggregates. This should be considered when cell aggregates instead of melanospheres are used in the study of melanoma biology and cell response to drugs.

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“…[15][16][17][18] In recent research, lots of biomarkers including ABCB5 (ATP-binding cassette), 19,20 NGFR (nerve growth factor receptor, CD271) 21 and ALDH (aldehyde dehydrogenase) 22 were used to identify melanoma stem cells. However, it should be noted that CD271-positive cells were proven to be "genuine cancer stem cells" by Boiko et al 21 and Civenni.…”

mentioning

confidence: 99%

“…[39][40][41][42][43][44] It was reported that SOX10 could maintain the multipotency of melanoma stem cells, the tumorigenic and proliferation and metastasis of melanoma cells. [19][20][21] In some reports, both CD271 and SOX10 were identified as melanoma stem cell biomarkers to evaluate stemness of melanoma cells. 23 In this study, the downregulation of CD271 and SOX10 expression resulting from the CONP treatment further supported CONPs have much more superiority in suppressing stemness of melanoma cells and killing melanoma stem cells than some other antitumor drugs.…”

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confidence: 99%

Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells

Wang²,

et al. 2017

IJN

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Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271 +/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271 +/high cells could accumulate more CONPs than CD271 −/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD271, SOX10 and MITF. These results above proved the effectiveness of CONPs in inhibiting melanoma progress through multiple pathways, especially through targeting melanoma stem cells.

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ABCB5 Maintains Melanoma-Initiating Cells through a Proinflammatory Cytokine Signaling Circuit

Cited by 122 publications

References 50 publications

Transient TNF regulates the self-renewing capacity of stem-like label-retaining cells in sphere and skin equivalent models of melanoma

Transient TNF regulates the self-renewing capacity of stem-like label-retaining cells in sphere and skin equivalent models of melanoma

Phenotypic diversity of patient-derived melanoma populations in stem cell medium

Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells

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