The vitamin D receptor is widely expressed in bone metastases from various types of primary tumors

Introduction Bone metastases frequently occur in late-stage cancers, particularly of prostate and breast carcinomas. Generally, metastatic tumor treatment is predominantly restricted to palliative measures. Further, bone metastases reduce patient’s quality of life due to skeletal-related events. Vitamin D has been demonstrated to exert anti-proliferative, pro-apoptotic and pro-differentiation effects on many cancer cells and is often deficient in patients with bone tumors. These direct effects of vitamin D are mostly mediated through binding to the vitamin D receptor (VDR), a nuclear hormone receptor. Notably, a high VDR expression in primary tumors is inversely associated to aggressive tumor characteristics. Moreover, it has been demonstrated that the VDR has a ligand-independent function in cancer cells affecting tumor growth and the metastatic potential to bone. However, there are currently no reports of studies investigating VDR expression and vitamin D metabolism in bone metastases. For this reason, the aim was to assess VDR expression in various types of bone metastases secondary to prostate-, breast-, kidney-, lung-, follicular thyroid- and colorectal cancer.

Methods The VDR and the vitamin D catabolizing enzyme CYP24A1 protein level expression was examined in bone metastases paraffin sections of 66 patients with different cancer types using immunohistochemistry. Expression levels were graded independently and blindly. Following an established scoring system, consisting of the percentage of tumour cells stained and the assessment for intensity of the staining, the expression levels were evaluated and correlated to patient data, especially tumor characteristics.

Results The VDR was detected and rated positive in 54 of 66 bone metastases (81%) and CYP24A1 in 40/66 (61%). While the VDR was localized in the nucleus and cytoplasm, CYP24A1 was identified in the cytoplasm only. VDR and CYP24A1 expression showed a significant positive correlation. Interestingly, patients with further metastases besides bone metastases had reduced VDR and CYP24A1 protein levels compared to patients without other metastases. Further, there was no significant correlation of the tumors histochemical and clinical characteristics such as grading or T-stage and VDR or CYP24A1 expression.

Discussion We detected a wide expression of the VDR in various types of bone metastases. This clearly points to a potential role of vitamin D signaling in bone metastases. As vitamin D deficiency is frequent in patients with bone metastases, vitamin D supplementation might be of great importance for these patients.

Keywords vitamin D receptor, bone metastasis, cancer biology, Immunohistochemistry

Korrespondenzadresse Jonas Seiler, Julius-Maximilians-Universität Würzburg, Bernhard-Heine-Centrum für Bewegungsforschung, Friedrich-Bergius-Ring 15, 97076 Würzburg, Deutschland, E-Mail: [e-mail]

Publication History

Article published online:
08 September 2022