The Synthesis of Vitamin D Metabolites by Human Melanoma Cells*

Frankel, Theresa L.; Mason, Rebecca S.; Hersey, Peter; Murray, Elaine; Posen, Solomon

doi:10.1210/jcem-57-3-627

Cited by 42 publications

(18 citation statements)

References 25 publications

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“…Although it is clear that the kidney is the main site of production of l,25(OH)2D3, cell lines de¬ rived from bone (Howard et al 1981) and skin (Frankel et al 1983) have demonstrable activities of the 25(OH)D3-l-hvdroxvlase enzyme. Indeed, low plasma concentrations of 1,25(OH)2D3 have been demonstrated in anephric patients (Lambert et al 1982), and it has been suggested that granulomatous tissue mav be a site of l,25(OH)2D3 synthesis (Barbour et al 1981).…”

Section: Discussionmentioning

confidence: 99%

Circulating vitamin D metabolites and hypercalcaemia of malignancy

Ralston¹,

Cowan²,

Robertson³

et al. 1984

Acta Endocrinologica

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Plasma concentrations of 1.25 dihvdroxvcholecalciferol were measured in 44 patients with malignancy associated hvpercalcaemia and related to other hormonal regulators of calcium metabolism. Immunoreactive PTH concentrations were suppressed in all but 2 patients and, as a group, patients with hvpercalcaemia of malignancy had lower 1,25 dihydroxycholecalciferol concentrations than normocalcaemic cancer patients.1,25 dihydroxycholecalciferol concentrations were clearly detectable in a significant proportion (43%) of hypercalcaemia cases however, suggesting that in these patients the active vitamin D metabolite may contribute to the pathogenesis and maintenance of the hypercalcaemia by stimulating bone resorption, and/or by increasing absorption of calcium from the intestine. Measurement of plasma 1,25 dihydroxycholecalciferol concentration does not provide a wholly reliable method for distinguishing the hypercalcaemia of malignancy from primary hyperparathyroidism.It has recently been established that in many pa¬ tients with malignancy associated hypercalcaemia, evidence can be found for a humoral aetiology, whether or not bone métastases are present

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Section: Discussionmentioning

confidence: 99%

Circulating vitamin D metabolites and hypercalcaemia of malignancy

Ralston¹,

Cowan²,

Robertson³

et al. 1984

Acta Endocrinologica

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“…239 This observation was supported by the description of vitamin D metabolism in melanoma cells. 240,241 Further studies showed that vitamin D inhibited the growth of several melanoma cell lines, including: human: A375, 242 ME18, 243 MeWo, 244–246 RPMI 7951, 247,248 SK Mel 28, 247,249,250 SKMEL-188, WM35 and WM1341; 39,40,64,118,119,242,251 mouse B16; 67,252,253 and hamster Bomirski melanomas. 67,118 Furthermore, 1,25(OH) 2 D3 inhibited anchorage-independent growth and plating efficiency of human SKMEL-188, hamster AbC1, 39,64,118 and murine B16 (ref.…”

Section: Vitamin D and Experimental Models Of Melanomamentioning

confidence: 99%

Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management

Slominski

Brożyna

Żmijewski

et al. 2017

Laboratory Investigation

117

128

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Ultraviolet B (UVB), in addition to having carcinogenic activity, is required for the production of vitamin D3 (D3) in the skin which supplies >90% of the body's requirement. Vitamin D is activated through hydroxylation by 25-hydroxylases (CYP2R1 or CYP27A1) and 1α-hydroxylase (CYP27B1) to produce 1,25(OH)2D3, or through the action of CYP11A1 to produce mono-di- and trihydroxy-D3 products that can be further modified by CYP27B1, CYP27A1, and CYP24A1. The active forms of D3, in addition to regulating calcium metabolism, exert pleiotropic activities, which include anticarcinogenic and anti-melanoma effects in experimental models, with photoprotection against UVB-induced damage. These diverse effects are mediated through an interaction with the vitamin D receptor (VDR) and/or as most recently demonstrated through action on retinoic acid orphan receptors (ROR)α and RORγ. With respect to melanoma, low levels of 25(OH)D are associated with thicker tumors and reduced patient survival. Furthermore, single-nucleotide polymorphisms of VDR and the vitamin D-binding protein (VDP) genes affect melanomagenesis or disease outcome. Clinicopathological analyses have shown positive correlation between low or undetectable expression of VDR and/or CYP27B1 in melanoma with tumor progression and shorter overall (OS) and disease-free survival (DFS) times. Paradoxically, this correlation was reversed for CYP24A1 (inactivating 24-hydroxylase), indicating that this enzyme, while inactivating 1,25(OH)2D3, can activate other forms of D3 that are products of the non-canonical pathway initiated by CYP11A1. An inverse correlation has been found between the levels of RORα and RORγ expression and melanoma progression and disease outcome. Therefore, we propose that defects in vitamin D signaling including D3 activation/inactivation, and the expression and activity of the corresponding receptors, affect melanoma progression and the outcome of the disease. The existence of multiple bioactive forms of D3 and alternative receptors affecting the behavior of melanoma should be taken into consideration when applying vitamin D management for melanoma therapy.

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“…Moreover, several anticancer mechanisms of calcitriol have been demonstrated, including local production of calcitriol by tumor cells (Frankel et al, 1983), with calcitriol resulting in increased tumor cell differentiation (Mason et al, 1988), increased tumor cell apoptosis (Ravid et al, 1999) and reduced tumor-induced angiogenesis (Majewski et al, 1996).…”

Section: Non-classical Effects Of Vitamin Dmentioning

confidence: 99%

Vitamin D: the light side of sunshine

2011

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Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

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The Synthesis of Vitamin D Metabolites by Human Melanoma Cells*

Cited by 42 publications

References 25 publications

Circulating vitamin D metabolites and hypercalcaemia of malignancy

Circulating vitamin D metabolites and hypercalcaemia of malignancy

Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management

Vitamin D: the light side of sunshine

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