Mouse models of UV-induced melanoma: genetics, pathology, and clinical relevance

Day, Chi-Ping; Marchalik, Rachel; Merlino, Glenn; Michael, Helen

doi:10.1038/labinvest.2016.155

Cited by 38 publications

(32 citation statements)

References 76 publications

(82 reference statements)

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“…Artificial sources of UV such as solar lamps, tanning beds and UV-based therapies have been reported to be linked to melanoma development (48,(60)(61)(62)(63)(64)(65)(66)(67). It is unclear whether UVB or UVA plays a major role in melanomagenesis (58,(68)(69)(70)(71).…”

Section: Introduction To the Ultraviolet B (Uvb) In Skin Biology: A Tmentioning

confidence: 99%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma. Skin cells are able to activate vitamin D via classical and nonclassical metabolic pathways (1-9). Vitamin D derivatives have anticancer properties and promote differentiation and inhibit proliferation of various cells, including melanoma, the most aggressive and lethal type of skin cancer. In this review, we provide an overview on the endogenous synthesis and activation of vitamin D via classical and non-classical pathways. We also present the association of vitamin D and melanoma based on epidemiological, experimental and clinical evidence, showing that defects in vitamin D signaling correlate with progression of melanoma and disease outcome. Therefore, restoration of the adequate vitamin D signaling can play a role in melanoma therapy. 473 This article is freely accessible online.

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Section: Introduction To the Ultraviolet B (Uvb) In Skin Biology: A Tmentioning

confidence: 99%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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“…Most of these models were based on the development of transgenic animal models. Two recent review papers have given a detailed analysis of the mouse models of melanoma [ 187 , 188 ]. Targeted deletion of the CDKN2A locus induced the development of various tumors, but not of melanomas.…”

Section: Animal Models Of Melanomamentioning

confidence: 99%

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

Testa

Castelli

2017

Medical Sciences

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Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

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“…Melanin production in skin is important for protecting cutaneous cellular nuclei from harmful ultraviolet radiation (UVR), which is the most ubiquitous known carcinogen. Exposure to UVR has been associated with benign nevi, melanocytic lesions, and malignant melanomas [ 1 , 2 ]. It is necessary to fully understand the biology of melanocytes and their response to UVR exposure as well as the indirect consequences of UVR on melanocytes by promoting changes in the skin microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Labeling of Melanocytes in Mice

Preston

Aras

Zaidi

2018

IJMS

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Melanocytes are pigment producing cells in the skin that give rise to cutaneous malignant melanoma, which is a highly aggressive and the deadliest form of skin cancer. Studying melanocytes in vivo is often difficult due to their small proportion in the skin and the lack of specific cell surface markers. Several genetically-engineered mouse models (GEMMs) have been created to specifically label the melanocyte compartment. These models give both spatial and temporal control over the expression of a cellular ‘beacon’ that has an added benefit of inducible expression that can be activated on demand. Two powerful models that are discussed in this review include the melanocyte-specific, tetracycline-inducible green fluorescent protein expression system (iDct-GFP), and the fluorescent ubiquitination-based cell cycle indicator (FUCCI) model that allows for the monitoring of the cell-cycle. These two systems are powerful tools in studying melanocyte and melanoma biology. We discuss their current uses and how they could be employed to help answer unresolved questions in the fields of melanocyte and melanoma biology.

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Mouse models of UV-induced melanoma: genetics, pathology, and clinical relevance

Cited by 38 publications

References 76 publications

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

Spatiotemporal Labeling of Melanocytes in Mice

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