Vitamin D2026-07

Vitamin D deficiency alters prostate epithelial differentiation and increases prostate cancer aggressiveness in ex vivo and in vivo models.

Duraki Adriana, Krieger Kirsten D, Celada Sasha, Holt Robert A et al. — Cancer letters

Summary

This study explores how low vitamin D levels might impact prostate health. Researchers found that a lack of vitamin D could disrupt the normal development of prostate cells and potentially make prostate cancer more aggressive in laboratory and animal models. These findings highlight vitamin D's important role in prostate biology and suggest it could be a factor in prostate cancer risk.

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Key points

Vitamin D deficiency can disrupt the normal development of prostate cells.
Low vitamin D levels might increase the aggressiveness of prostate cancer.
The study used both lab-based cell models and animal models to investigate these effects.
Maintaining adequate vitamin D levels may be important for overall prostate health.

What the study looked at

What question the study asked: This study investigated how vitamin D deficiency affects the normal development of prostate cells and potentially influences the aggressiveness of prostate cancer. How it was studied (design/participants): Researchers used a multi-faceted approach. They examined mouse prostate organoids, which are miniature prostate tissues grown in a lab, and studied mice fed a diet lacking vitamin D. Additionally, they cultured human prostate cancer cells (MDA-PCa-2b and 22Rv1) and observed their responses to both short-term and long-term exposure to vitamin D. Advanced techniques like single-cell RNA sequencing were employed to analyze gene expression changes. What it found: The study revealed that vitamin D deficiency significantly impaired the normal differentiation of prostate cells in mice, an effect more pronounced than that caused by androgen deficiency. In mice, low vitamin D altered the expression of genes sensitive to male hormones within prostate cells. For human prostate cancer cells, long-term vitamin D exposure had distinct effects compared to short-term treatment; notably, some cancer cells lost their ability to form tumors in animal models, even while proliferating normally in vitro. These findings underscore vitamin D's critical role in both healthy prostate function and cancer progression by influencing cell development and signaling pathways.

Dietary takeaway

While this study provides valuable insights from lab and animal models, it's important to remember that human studies are needed to confirm these findings definitively. However, maintaining adequate vitamin D levels through diet and safe sun exposure is generally recommended for overall health. Foods like fatty fish (salmon, mackerel), fortified milk and cereals, and some mushrooms are good dietary sources of vitamin D, which may contribute to prostate health.

Abstract

Here, we examined the consequences of biologically relevant vitamin D deficiency, a known risk factor for aggressive prostate cancer, using ex vivo and in vivo models. Phenotypic and single-cell RNA sequencing of mouse prostate organoids showed that vitamin D deficiency stunted luminal cell differentiation more than androgen deficiency, which is a known driver of prostate development. Mice fed a vitamin D-deficient diet showed significantly altered expression of androgen-responsive genes in their prostate luminal cells, as determined by single-cell RNA sequencing. MDA-PCa-2b and 22Rv1 human prostate cancer cells, when maintained for 6 months in 1,25-dihydroxyvitamin D, had very different responses compared to short-term treatments. Notably, the MDA-PCa-2b cells lost the ability to form xenografts, despite normal proliferation in vitro. RNA sequencing showed that these cells also had disruptions in androgen signaling and in multiple cancer-related pathways, which differed by treatment duration. This study offers new insights and validation of vitamin D's role in both benign and malignant prostate biology, underscoring its essential hormonal functions and supporting strategies for vitamin D supplementation to reduce prostate cancer risk in vulnerable populations.

View on PubMed →DOI: 10.1016/j.canlet.2026.218732