Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Brożyna, Anna A.; Hoffman, Robert M.; Słomiński, Andrzej

doi:10.21873/anticanres.13976

Cited by 53 publications

(55 citation statements)

References 220 publications

(246 reference statements)

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“…One of them is the protection of VDR-defective human fibroblasts against DNA damage induced by UV mediated by the endoplasmic reticulum stress protein 57 (ERP57, MARRS) [18]. Therefore, the anticancer effects of vitamin D may be underlined by both genomic and non-genomic actions as UV-induced DNA damages, including cyclobutane dimers and (6-4)-photoproducts, are observed in skin cancers (reviewed in [19]).…”

Section: Vitamin D-an Essential Nutrient and A Potential Preventive Amentioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.

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Section: Vitamin D-an Essential Nutrient and A Potential Preventive Amentioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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“…Since vitamin D also exhibits antiproliferative and pro-differentiating properties, its deficiency has been correlated with the progression of several malignancies [ 70 , 215 , 216 , 217 , 218 , 219 ], especially breast [ 220 , 221 , 222 , 223 ], ovarian [ 224 , 225 ] and skin tumours [ 226 , 227 , 228 , 229 ].…”

Section: Vitamin D: State Of the Artmentioning

confidence: 99%

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi

Perrone

Napolitano

et al. 2020

Cancers

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Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production—occurring in the skin and dependent on sun exposure—contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.

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“…Previously, we found that changes in the expression of VDR, RORα, RORγ, CYP27B1 and CYP24A1 in melanomas correlate with melanoma progression and may affect the disease outcome . In addition, active melanogenesis stimulates the expression of HIF‐1α and HIF‐dependent pathways .…”

Section: Introductionmentioning

confidence: 96%

On the relationship between VDR, RORα and RORγ receptors expression and HIF1‐α levels in human melanomas

Brożyna

Jóźwicki

Jetten

et al. 2019

Experimental Dermatology

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We analysed the correlation between the expression of HIF‐1α (hypoxia‐inducible factor 1 alpha), the nuclear receptors: VDR (vitamin D receptor), RORα (retinoic acid receptor‐related orphan receptor alpha), and RORγ and CYP24A1 (cytochrome P450 family 24 subfamily A member 1) and CYP27B1 (cytochrome P450 family 27 subfamily B member 1), enzymes involved in vitamin D metabolism. In primary and metastatic melanomas, VDR negatively correlated with nuclear HIF‐1α expression (r = −.2273, P = .0302; r = −.5081, P = .0011). Furthermore, the highest HIF‐1α expression was observed in pT3‐pT4 VDR‐negative melanomas. A comparative analysis of immunostained HIF‐1α and CYP27B1 and CYP24A1 showed lack of correlation between these parameters both in primary tumors and melanoma metastases. In contrast, RORα expression correlated positively with nuclear HIF‐1α expression in primary and metastatic lesions (r = .2438, P = .0175; r = .3662, P = .0166). Comparable levels of HIF‐1α expression pattern was observed in localized and advanced melanomas. RORγ in primary melanomas correlated also positively with nuclear HIF‐1α expression (r = .2743, P = .0129). HIF‐1α expression was the lowest in localized RORγ‐negative melanomas. In addition, HIF‐1α expression correlated with RORγ‐positive lymphocytes in melanoma metastases. We further found that in metastatic lymph nodes FoxP3 immunostaining correlated positively with HIF‐1α and RORγ expression in melanoma cells (r = .3667; P = .0327; r = .4208, P = .0129). In summary, our study indicates that the expression of VDR, RORα and RORγ in melanomas is related to hypoxia and/or HIF1‐α activity, which also affects FoxP3 expression in metastatic melanoma. Therefore, the hypoxia can affect tumor biology by changing nuclear receptors expression and molecular pathways regulated by nuclear receptors and immune responses.

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Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Cited by 53 publications

References 220 publications

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

On the relationship between VDR, RORα and RORγ receptors expression and HIF1‐α levels in human melanomas

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