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Abstract

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.

Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

“…Given the effects of VDR on limiting cell proliferation, as well as its putative tumor-suppressor role in the skin, as demonstrated by animal studies (9,10), this increased VDR expression in the neoplasms seems paradoxical. However, increased VDR expression has also been observed in other malignancies (23–25). VDR expression in normal oral epithelium is confined to the basal cell layer, which represents the epithelial compartment with proliferating cells.…”

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

“…Published papers hypothesize that calcitriol enhances VDR expression at gene and protein levels in vitro in renal and various non-renal tissues in the body, including the colon [ 44 , 45 ], breast [ 46 , 47 ] and prostrate [ 48 ]. Moreover, it is thought that inflammatory peptides/cytokines expressed by tumor-infiltrating leukocytes and oral premalignant/ tumor cells also up-regulate VDR expression in adjacent cells [ 49 ].…”

Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

“…It can be speculated whether the increased content of VDR on the mRNA and protein levels that we have shown in this study is due to an increased formation of calcitriol in these tumour cells. Moreover, inflammatory peptides/cytokines expressed by tumour-infiltrating leucocytes and oral precancerous/tumor cells may upregulate VDR expression in adjacent cells ( 51 ).…”

“…Therefore, we perfomed correlation analysis of serum vitamin d levels and the corresponding VDR in the tumor tissue of OSCC patients but the data did not show any significant correlation. This can be explained as many cytokines and inflammatory peptides excreted by tumour-infiltrating leucocytes as well as tumour cells may influence VDR expression ( 51 ).…”