ATP-binding Cassette Transporter ABCB5 Gene is Expressed with Variability in Malignant Melanoma

Vásquez-Moctezuma, Ismael; Meraz-Ríos, Marco Antonio; Villanueva-López, C.G.; Magaña, Mario; Martínez-Macías, R; Sánchez-González, Dolores Javier; Garcı́a-Sierra, Francisco; Herrera-González, Norma Estela

doi:10.1016/j.ad.2009.12.006

Cited by 21 publications

(11 citation statements)

References 29 publications

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“…However, we (as well as other groups [62]) did not observe consistent but highly variable expression of ABCB5 in the melanoma SP. Differences in experimental setup may be responsible; Luo et al [10] studied gene expression of ABC transporters in SP cells of melanoma xenografts whereas our analyses were done on the SP of melanoma samples directly from the patient.…”

Section: Discussioncontrasting

confidence: 65%

The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis

et al. 2013

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Melanoma remains the most lethal skin cancer, mainly because of high resistance to therapy. Side population (SP) cells are found in many types of cancer and are usually enriched in therapy-resistant as well as tumorigenic cells. Here, we identified a Hoechst dye-effluxing SP in a large series of human melanoma samples representing different progression phases. The SP size did not change with disease stage but was correlated with the prognostic “Breslow’s depth” in the primary (cutaneous) tumors. When injected into immunodeficient mice, the SP generated larger tumors than the bulk “main population” (MP) melanoma cells in two consecutive generations, and showed tumorigenic capacity at lower cell numbers than the MP. In addition, the SP reconstituted the heterogeneous composition of the human A375 melanoma cell line, and its clonogenic activity was 2.5-fold higher than that of the MP. Gene-expression analysis revealed upregulated expression in the melanoma SP (versus the MP) of genes associated with chemoresistance and anti-apoptosis. Consistent with these molecular characteristics, the SP increased in proportion when A375 cells were exposed to the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating condition of hypoxia. In addition, the SP showed enhanced expression of genes related to cell invasion and migration, as well as to putative (melanoma) cancer stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected in a number of tumor cells in human melanomas, and in particular in clusters at the invasive front of the primary tumors. Together, our findings support that the human melanoma SP is enriched in tumorigenic and chemoresistant capacity, considered key characteristics of CSC. The melanoma SP may therefore represent an interesting therapeutic target.

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Section: Discussioncontrasting

confidence: 65%

The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis

et al. 2013

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“…Clinical data support a role for ABCB5, in that expression of ABCB5 is linked to disease progression. Expression of ABCB5 is generally low in pigmented melanocytic nevus tissue, but is found in a subpopulation of thick primary melanomas and metastases (104, 108, 109). Furthermore, induction of terminal differentiation is correlated with decreasing levels of ABCB5 (110).…”

Section: Melanoma Stem Cellsmentioning

confidence: 99%

Melanocytes, melanocyte stem cells, and melanoma stem cells

Lang¹,

Mascarenhas²,

Shea³

2013

Clinics in Dermatology

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Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, while the latter play an active role in a lethal form of cancer. These two cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing non-tumor cells.

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“…Indeed, well before the discovery and experimental authentication of melanoma stem cells, Hendrix and co-workers noted differentiation heterogeneity in melanomas in the form of endothelial gene expression by tumor cells (Maniotis et al, 1999). This phenomenon, known as vasculogenic mimicry, was posited to be the consequence of differentiation plasticity in primitive, stem-like melanoma cells (Hendrix et al, 2003b), a prediction that more recently has been validated using melanoma stem cell biomarkers and experimental systems and clinical tissues (Boiko et al, 2010; Civenni et al, 2011; Fang et al, 2005; Klein et al, 2007; Monzani et al, 2007; Rappa et al, 2008; Schatton et al, 2008; Sharma et al, 2010; Vasquez-Moctezuma et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Stem cells and targeted approaches to melanoma cure

Murphy

Wilson

Girouard

et al. 2014

Molecular Aspects of Medicine

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Melanoma stem cells, also known as malignant melanoma-initiating cells, are identifiable through expression of specific biomarkers such as ABCB5 (ATP-binding cassette, sub-family B (MDR/TAP), member 5), NGFR (nerve growth factor receptor, CD271) and ALDH (aldehyde dehydrogenase), and drive melanoma initiation and progression based on prolonged self-renewal capacity, vasculogenic differentiation and immune evasion. As we will review here, specific roles of these aggressive subpopulations have been documented in tumorigenic growth, metastatic dissemination, therapeutic resistance, and malignant recurrence. Moreover, recent findings have provided pre-clinical proof-of-concept for the potential therapeutic utility of the melanoma stem cell concept. Therefore, melanoma stem cell-directed therapeutic approaches represent promising novel strategies to improve therapy of this arguably most virulent human cancer.

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ATP-binding Cassette Transporter ABCB5 Gene is Expressed with Variability in Malignant Melanoma

Cited by 21 publications

References 29 publications

The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis

The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis

Melanocytes, melanocyte stem cells, and melanoma stem cells

Stem cells and targeted approaches to melanoma cure

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