The following is a summary of “Dual effect of vitamin D3 on breast cancer-associated fibroblasts,” published in the February 2024 issue of Oncology by Łabędź et al.
Cancer-associated fibroblasts (CAFs) wield significant influence within the tumor microenvironment, yet the impact of vitamin D3 (VD3) on breast CAFs remains largely unexplored. This study delves into the ex vivo effects of calcitriol, an active form of VD3, on CAFs isolated from breast cancer tissues.
Isolated CAFs were exposed to varying concentrations of calcitriol, and their phenotype, gene expression, protein levels, and secretory profiles were evaluated. Furthermore, conditioned media (CM) from calcitriol-treated CAFs were utilized to assess their influence on the migration and protein expression of MCF-7 and MDA-MB-231 breast cancer cells.
Patients deficient in VD3 displayed altered levels of key proteins, such as β-catenin, TGFβ1, and CYP24A1, along with distinct CAF infiltration patterns compared to VD3-normal patients. Calcitriol treatment demonstrated dose-dependent effects on CAF viability, with a weaker impact observed in premenopausal and VD3-normal patients. Notably, calcitriol downregulated the expression of certain genes associated with CAF function while modulating the secretion and activity of various proteins involved in tumor progression. Moreover, CM from calcitriol-treated CAFs exhibited differential effects on breast cancer cells’ migration and protein expression profiles, influenced by patient menopausal status and VD3 levels.
Calcitriol exerts multifaceted effects on breast CAFs, with implications for their immunosuppressive or pro-cancer properties. While specific molecular changes suggest an anticancer phenotype in response to calcitriol, the overall impact remains complex. Nonetheless, CM from calcitriol-treated CAFs demonstrated a trend toward decreased migration in breast cancer cells, particularly in nonmetastatic and postmenopausal patients. These findings shed light on the intricate interplay between VD3 and breast CAFs, underscoring the potential of calcitriol as a modulator of the tumor microenvironment in breast cancer.
Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11961-z