Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
Keywords: 1,25(OH)2D3, 1α,25-dihydroxyvitamin D3; 1α,25-Dihydroxyvitamin D3; 25(OH)D, 25-hydroxyvitamin D; CAF, cancer-associated fibroblast; CRC, colorectal cancer; CSC, cancer stem cell; Cancer stem cell; Cancer-associated fibroblast; DBP/GC, vitamin D-binding protein; ESCC, esophageal squamous cell carcinoma; GI, gastrointestinal; NSCLC, non-small cell lung cancer; PC, pancreatic adenocarcinoma; PG, prostaglandin; PSC, pancreatic stellate cells; TDEC, tumor derived endothelial cell; TIC, tumor initiating cell; TIL, tumor-infiltrating lymphocyte; TME, tumor microenvironment; Tumor microenvironment; Tumor-derived endothelial cell; Tumor-infiltrating lymphocyte; VDR, vitamin D receptor; VDRE, VDR element; VEGF, vascular endothelial growth factor; Vitamin D.