In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor.
Emerging evidence suggests that the normally tight balance between CYP27B1 and CYP24A1 becomes deregulated during cancer development, leading to abrogation of the tumor suppressive effects triggered by VDR.
VDR expression was inversely related to aggressive tumor characteristics, including large tumor size, hormonal receptor (HR) negativity, and triple-negative subtype (P < 0.05).
We found that ablation of vitamin D receptor expression within BCa cells accelerates primary tumor growth and enables the development of metastases, demonstrating a tumor autonomous effect of vitamin D signaling to suppress BCa metastases.
Subgroup analyses showed that significantly association was existed in Caucasian population, the subgroup of population-based controls and the stratified group with advanced tumor.These results indicate that the VDR Fok I polymorphism might be capable of causing PCa susceptibility and could be a promising target to forecast the PCa risk for clinical practice.
Heterogeneity by tumour subtype was seen for three VDR polymorphisms (rs1544410, rs7967152 and rs2239186) among Europeans, in which associations with ER-/PR-/HER2+ tumours, but not with other subtypes, were observed.
We evaluated the associations of the FOK1 and Taq1 VDR polymorphisms and breast cancer risk and possible effect modification by steroid receptor status of the tumor.
Interestingly, increasing evidence now demonstrates an important function of the vitamin D endocrine system (VDES) for prevention of BCC, SCC and melanoma, identifying the vitamin D receptor as a tumor suppressor in the skin.
We found that several well-known oncogenes, including H19, HOTTIP and Nespas, are significantly increased (6.3-1.8-fold), whereas tumor suppressors (Kcnq1ot1, lincRNA-p21) are decreased (up to 50-70%) in VDR deleted keratinocytes.
Therefore, these findings indicate that the search for mechanisms to sensitize prostate cancer cells to the antiproliferative effects of VDR ligands needs to account for the impact of VDR activity in the tumor microenvironment.
These data highlight a potential application of VDR-based therapies for the reduction of growth-promoting androgens within the tumor micro-environment.
Vitamin D signalling (VDS) protects against skin cancer as demonstrated by the susceptibility of the skin to tumor formation in VDR null mice and protection from UVB-induced mutations when VDR agonists are administered.
In this chapter we will first discuss recent data regarding potential mechanisms by which vitamin D signaling suppresses tumor formation, then focus on three general mechanisms that mediate tumor suppression by VDR in the skin: inhibition of proliferation and stimulation of differentiation, immune regulation, and stimulation of DNA damage repair (DDR).
Importantly, nuclear levels of CTSL, vitamin D receptor, and 53BP1 emerged as a novel triple biomarker signature for stratification of patients with BRCA1-mutated tumors and TNBC, with potential predictive value for drug response.
(i) Measure the expression of CYP27B1, CYP24A1, and vitamin D3 receptor in human nonmalignant and cholangiocarcinoma lines and biopsy control or tumour samples; and (ii) evaluate the effects of vitamin D3 on vitamin D3 synthesis and cholangiocarcinoma growth.
Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers.