Analysis of the vitamin D system in cutaneous squamous cell carcinomas.

Abstract

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.

• Authors: Jörg Reichrath, Leyla Rafi, Martin Rech, Tanja Mitschele, Viktor Meineke, Barbara C Gärtner, Wolfgang Tilgen, Michael F Holick
• Journal: Journal of cutaneous pathology (J Cutan Pathol) Vol. 31 Issue 3 Pg. 224-31 (Mar 2004) ISSN: 0303-6987 [Print] United States
• PMID: 14984574 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• Receptors, Calcitriol
• Steroid Hydroxylases
• CYP27A1 protein, human
• Cholestanetriol 26-Monooxygenase
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• Calcitriol

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (biosynthesis)
• Apoptosis (physiology)
• Calcitriol (pharmacology, physiology)
• Carcinoma, Squamous Cell (physiopathology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cholestanetriol 26-Monooxygenase
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• RNA, Messenger (analysis)
• Receptors, Calcitriol (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (physiopathology)
• Steroid Hydroxylases (biosynthesis)