From Melanocyte to Metastatic Malignant Melanoma

Bandarchi, Bizhan; Ma, Linglei; Navab, Roya; Seth, Arun; Rasty, Golnar

doi:10.1155/2010/583748

Cited by 115 publications

(104 citation statements)

References 107 publications

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“…To assess changes in gene expression associated with anchorage-independent growth, we isolated RNA from the melanocyte colonies that grew in soft agar and examined a panel of melanoma and cancer-specific markers by TaqMan reverse transcriptase PCR (Figure 10). Consistent with expectation (Hoek et al, 2004;Kuphal et al, 2006;Klein et al, 2007;Palmieri et al, 2009;Bandarchi et al, 2010), miR-506-514 overexpression and growth in soft agar was associated with substantial downregulation of E-cadherin, P-cadherin, p16/CDKN2A, DKK3, RAB33A, TYRP1 and BAD, as well as greatly increased expression of Ki67, MIA, DCT and the stem cell markers PROM1/ CD133 and Nestin. Other genes showed no changes in expression due to altered miR-506-514 levels.…”

Section: Resultssupporting

confidence: 73%

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

et al. 2011

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Malignant melanoma is the most aggressive form of skin cancer and its incidence has doubled in the last two decades. It represents only 4% of skin cancer cases per year, but causes as many as 74% of skin cancer deaths. Early detection of malignant melanoma is associated with survival rates of up to 90%, but later detection (stage III to stage IV) is associated with survival rates of only 10%. Dysregulation of microRNA (miRNA) expression has been linked to tumor development and progression by functioning either as a tumor suppressor, an oncogene or a metastasis regulator in multiple cancer types. To understand the role of miRNA in the pathogenesis of malignant melanoma and identify biomarkers of metastasis, miRNA expression profiles in skin punches from 33 metastatic melanoma patients and 14 normal healthy donors were compared. We identified a cluster of 14 miRNAs on the X chromosome, termed the miR-506-514 cluster, which was consistently overexpressed in nearly all melanomas tested (30-60 fold, Po0.001), regardless of mutations in N-ras or B-raf. Inhibition of the expression of this cluster as a whole, or one of its sub-clusters (Sub-cluster A) consisting of six mature miRNAs, led to significant inhibition of cell growth, induction of apoptosis, decreased invasiveness and decreased colony formation in soft agar across multiple melanoma cell lines. Sub-cluster A of the miR-506-514 cluster was critical for maintaining the cancer phenotype, but the overexpression of the full cluster was necessary for melanocyte transformation. Our results provide new insights into the functional role of this miRNA cluster in melanoma, and suggest new approaches to treat or diagnose this disease.

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Section: Resultssupporting

confidence: 73%

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

et al. 2011

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“…Melanoma is a ma lignant tumour that arises from melanin-producing cells called melanocytes [1][2][3][4] . Approximately 90% of melanomas are cutaneous, but they can also occur at any anatomic location-for example, eye, mucosa, head and neck surfaces, and along the gastrointestinal and genitourinary tracts 2,5,6 .…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 90% of melanomas are cutaneous, but they can also occur at any anatomic location-for example, eye, mucosa, head and neck surfaces, and along the gastrointestinal and genitourinary tracts 2,5,6 . Cutaneous malignant melanoma (cmm) is responsible for the largest proportion (60% -80%) of skin cancer-related deaths 4,[7][8][9][10][11] . It was estimated that, in 2012, more than 232,000 people worldwide were diagnosed with cmm and more than 55,400 died of the disease 12 .…”

Section: Introductionmentioning

confidence: 99%

Burden of Illness for Metastatic Melanoma in Canada, 2011–2013

et al. 2016

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“…1,2 Due to the refractory responses to conventional cancer therapies, considerable energy has been devoted toward developing effective melanoma immunotherapeutic strategies. There is ample evidence that many melanoma tumor structures are immunogenic, and a growing number of melanoma-associated antigens are known targets for T-cell-mediated cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

A Screening Assay to Identify Agents That Enhance T-Cell Recognition of Human Melanomas

Haggerty

Dunn

Rose

et al. 2012

ASSAY and Drug Development Technologies

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Although a series of melanoma differentiation antigens for immunotherapeutic targeting has been described, heterogeneous expression of antigens such as Melan-A/MART-1 and gp100 results from a loss of antigenic expression in many late stage tumors. Antigen loss can represent a means for tumor escape from immune recognition, and a barrier to immunotherapy. However, since antigen-negative tumor phenotypes frequently result from reversible gene regulatory events, antigen enhancement represents a potential therapeutic opportunity. Accordingly, we have developed a cell-based assay to screen for compounds with the ability to enhance T-cell recognition of melanoma cells. This assay is dependent on augmentation of MelanA/MART-1 antigen presentation by a melanoma cell line (MU89). T-cell recognition is detected as interleukin-2 production by a Jurkat T cell transduced to express a T-cell receptor specific for an HLA-A2 restricted epitope of the Melan-A/MART-1 protein. This cellular assay was used to perform a pilot screen by using 480 compounds of known biological activity. From the initial proof-ofprinciple primary screen, eight compounds were identified as positive hits. A panel of secondary screens, including orthogonal assays, was used to validate the primary hits and eliminate false positives, and also to measure the comparative efficacy of the identified compounds. This cell-based assay, thus, yields consistent results applicable to the screening of larger libraries of compounds that can potentially reveal novel molecules which allow better recognition of treated tumors by T cells.

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From Melanocyte to Metastatic Malignant Melanoma

Cited by 115 publications

References 107 publications

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

Burden of Illness for Metastatic Melanoma in Canada, 2011–2013

A Screening Assay to Identify Agents That Enhance T-Cell Recognition of Human Melanomas

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