Analysis of the vitamin D system in cutaneous squamous cell carcinomas.
BACKGROUND
Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC).


METHODS
We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC.


RESULTS
Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1 alpha-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction.


CONCLUSIONS
Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors.
Reichrath
Jörg
J
Department of Dermatology, The Saarland University Hospital, Homburg, Germany. hajrei@uniklinik-saarland.de
Rafi
Leyla
L
Rech
Martin
M
Mitschele
Tanja
T
Meineke
Viktor
V
Gärtner
Barbara C
BC
Tilgen
Wolfgang
W
Holick
Michael F
MF
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D017209:Apoptosis / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D053493:Cholestanetriol 26-Monooxygenase; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000503:physiopathology*; D013250:Steroid Hydroxylases / Q000096:biosynthesis
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol