Identification of tumor-autonomous and indirect effects of vitamin D action that inhibit breast cancer growth and tumor progression

Abstract

Several epidemiological studies have found that low vitamin D levels are associated with worse prognosis and poorer outcomes in patients with breast cancer (BCa), although some studies have failed to find this association. In addition, prior research has found that BCa patients with vitamin D deficiency have a more aggressive molecular phenotype and worse prognostic biomarkers. As vitamin D deficiency is common in patients diagnosed with BCa, elucidating the cause of the association between poor outcomes and vitamin D deficiency promises to have a significant impact on improving care for patients with BCa including enabling the development of novel therapeutic approaches. Here we review our recent findings in this area, including our data revealing that reduction of the expression of the vitamin D receptor (Vdr) 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. We believe that these findings are likely relevant to humans as we discovered evidence that a mechanism of VDR regulation identified in our mouse models is conserved in human BCa. In particular, we identified a negative correlation between serum 25(OH)D concentration and the level of expression of the tumor progression factor ID1 in primary tumors from patients with breast cancer.

Keywords: Breast cancer; ID1; Metastasis; Microenvironment; Stromal cells; Vitamin D; Vitamin D receptor; calcitriol.