On the role of classical and novel forms of vitamin D in melanoma progression and management

Andrzej T. Slominski, Anna A. Brożyna, Cezary Skobowiat, Michal A. Zmijewski, Tae Kang Kim, Zorica Janjetovic, Allen S. Oak, Wojciech Jozwicki, Anton M. Jetten, Rebecca S. Mason, Craig Elmets, We Li, Robert M. Hoffman, Robert C. Tuckey

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume177
DOIs
Publication statusPublished - 1 Mar 2018

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Vitamin D
Melanoma
Cholecalciferol
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Cholesterol Side-Chain Cleavage Enzyme
Calcitriol Receptors
Calcitriol
Tretinoin
Polymorphism
Plating
Ultraviolet radiation
Carcinogens
Tumors
Skin
Carrier Proteins
Nucleotides
Genes
Planning
Enzymes
Proteins

Cite this

Slominski, Andrzej T. ; Brożyna, Anna A. ; Skobowiat, Cezary ; Zmijewski, Michal A. ; Kim, Tae Kang ; Janjetovic, Zorica ; Oak, Allen S. ; Jozwicki, Wojciech ; Jetten, Anton M. ; Mason, Rebecca S. ; Elmets, Craig ; Li, We ; Hoffman, Robert M. ; Tuckey, Robert C. / On the role of classical and novel forms of vitamin D in melanoma progression and management. In: Journal of Steroid Biochemistry and Molecular Biology. 2018 ; Vol. 177. pp. 159-170.
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title = "On the role of classical and novel forms of vitamin D in melanoma progression and management",
abstract = "Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.",
keywords = "Melanoma, Retinoic acid orphan receptors, Therapy, Vitamin D, Vitamin D receptor",
author = "Slominski, {Andrzej T.} and Brożyna, {Anna A.} and Cezary Skobowiat and Zmijewski, {Michal A.} and Kim, {Tae Kang} and Zorica Janjetovic and Oak, {Allen S.} and Wojciech Jozwicki and Jetten, {Anton M.} and Mason, {Rebecca S.} and Craig Elmets and We Li and Hoffman, {Robert M.} and Tuckey, {Robert C.}",
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Slominski, AT, Brożyna, AA, Skobowiat, C, Zmijewski, MA, Kim, TK, Janjetovic, Z, Oak, AS, Jozwicki, W, Jetten, AM, Mason, RS, Elmets, C, Li, W, Hoffman, RM & Tuckey, RC 2018, 'On the role of classical and novel forms of vitamin D in melanoma progression and management' Journal of Steroid Biochemistry and Molecular Biology, vol. 177, pp. 159-170. https://doi.org/10.1016/j.jsbmb.2017.06.013

On the role of classical and novel forms of vitamin D in melanoma progression and management. / Slominski, Andrzej T.; Brożyna, Anna A.; Skobowiat, Cezary; Zmijewski, Michal A.; Kim, Tae Kang; Janjetovic, Zorica; Oak, Allen S.; Jozwicki, Wojciech; Jetten, Anton M.; Mason, Rebecca S.; Elmets, Craig; Li, We; Hoffman, Robert M.; Tuckey, Robert C.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 177, 01.03.2018, p. 159-170.

Research output: Contribution to journalReview article

TY - JOUR

T1 - On the role of classical and novel forms of vitamin D in melanoma progression and management

AU - Slominski, Andrzej T.

AU - Brożyna, Anna A.

AU - Skobowiat, Cezary

AU - Zmijewski, Michal A.

AU - Kim, Tae Kang

AU - Janjetovic, Zorica

AU - Oak, Allen S.

AU - Jozwicki, Wojciech

AU - Jetten, Anton M.

AU - Mason, Rebecca S.

AU - Elmets, Craig

AU - Li, We

AU - Hoffman, Robert M.

AU - Tuckey, Robert C.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

AB - Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

KW - Melanoma

KW - Retinoic acid orphan receptors

KW - Therapy

KW - Vitamin D

KW - Vitamin D receptor

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