Dual effect of vitamin D on breast cancer-associated fibroblasts.

Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Despite the well-known in vitro antitumoral effect of vitamin D (VD), its impact on breast CAFs is almost unknown. In this study, we analyzed the ex vivo effects of calcitriol on CAFs isolated from breast cancer tissues.

Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse mammary gland cancer via the induction of proinflammatory cytokines.

Our research found that vitamin D (VD) treatment increased lung metastasis in mice with 4T1 murine breast cancer (BC). This study aims to investigate the impact of VD on the activation of tumor-associated macrophages (TAMs) in BC. Mice bearing 4T1, E0771, 67NR BC cells, and healthy mice, were fed diets with varying VD contents (100-deficient, 1000-normal, and 5000 IU/kg-elevated).

Age-Dependent Effect of Calcitriol on Mouse Regulatory T and B Lymphocytes.

The hormonally active vitamin D metabolite, calcitriol, functions as an important modulator of the immune system. We assumed that calcitriol exerts different effects on immune cells and cytokine production, depending on the age of the animal; therefore, we analyzed its effects on regulatory T lymphocytes and regulatory B lymphocytes in healthy young and old female C57Bl/6/Foxp3GFP mice. In the lymph nodes of young mice, calcitriol decreased the percentage of Tregs, including tTregs and pTregs, and the expression of GITR, CD103, and CD101; however, calcitriol increased the level of IL-35 in adipose tissue.

Modulation of Fibroblast Activity via Vitamin D Is Dependent on Tumor Type-Studies on Mouse Mammary Gland Cancer.

Vitamin D and its analogs are known to modulate the activity of fibroblasts under various disease conditions. However, their impact on cancer-associated fibroblasts (CAFs) is yet to be fully investigated. The aim of this study was to characterize CAFs and normal fibroblasts (NFs) from the lung of mice bearing 4T1, 67NR, and E0771 cancers and healthy mice fed vitamin-D-normal (1000 IU), -deficient (100 IU), and -supplemented (5000 IU) diets.

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models.

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)D analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study.