Overexpression of vitamin D receptor indicates a good prognosis for cholangiocarcinoma: implications for therapeutics.
BACKGROUND
Up-regulation of vitamin D receptor (VDR) expression has been shown in several tumors and is thought to represent an important endogenous response to tumor progression. The authors aimed to verify the expression of VDR and its clinical significance in histologically proven cholangiocarcinoma (CCA).


METHODS
The antiproliferative activity of vitamin D3 on CCA cell lines was explored. The immunohistochemistry of 111 paraffin-embedded CCA tissues showed that VDR expression gradually increased during CCA development. Normal bile duct epithelium rarely expresses VDR, whereas more than 74% of CCA tissues showed positive VDR staining, of which 40% were high. Approximately 80%-90%of CCA patients with papillary and well differentiated adenocarcinomas had positive VDR expression in tumor tissues, whereas 39% positive VDR expression was found in those with poorly differentiated CCAs (P < .001).


RESULTS
Expression of VDR was shown to be compatible with an overall favorable prognosis for CCA. Treatment with 1,25(OH)(2)D(3), an active metabolite of vitamin D3, in the CCA cell lines with high expression of VDR significantly reduced cell proliferation in a dose-dependent manner. The effect was not demonstrated in the CCA cell lines that had lower VDR expression.


CONCLUSIONS
These data indicated an active role for VDR in mediating the antiproliferative effects of 1,25(OH)(2)D(3) in CCA cell lines. VDR expression may constitute an important prerequisite for using vitamin D and/or its analogs in the treatment of CCA. Investigation of a mechanism by which VDR and its ligand mediate these processes is needed to provide the basis for the potential use of this hormone and its derivatives in the prevention and treatment of CCA.
Seubwai
Wunchana
W
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Wongkham
Chaisiri
C
Puapairoj
Anucha
A
Khuntikeo
Narong
N
Wongkham
Sopit
S
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001652:Bile Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002120:Calcium Channel Agonists; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol