Biology subjects

Vander Griend, D.

Publications and source records attributed to Vander Griend, D..

2 recordsLinked to original sources

bioRxiv2026

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

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 human prostate cancer cells, when maintained for 6 months in 1,25-dihydroxyvitamin D, lost the ability to form xenografts, despite normal proliferation in vitro. RNA sequencing showed that these cells also had disruptions in androgen signaling and multiple cancer-related pathways. This study offers new insights and validation of vitamin Ds 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. STATEMENT OF SIGNIFICANCEVitamin D is an essential hormone, however, the non-calcemic consequences of vitamin D deficiency remain poorly defined, despite its high prevalence in the population. This study demonstrates significant biological consequences of vitamin D deficiency on prostate cells at biologically relevant levels in multiple systems.

cancer biology↗

bioRxiv2021

Vitamin D deficiency increases prostatic megalin expression and globulin-bound testosterone import, increasing prostatic androgens in African American men

Vitamin D deficiency is associated with an increased risk of prostate cancer (PCa) mortality and is hypothesized to contribute to PCa aggressiveness and disparities in African American populations. The prostate epithelium was recently shown to express megalin, an endocytic receptor that internalizes globulin-bound hormones, which suggests regulation of prostate hormone levels, in contrast to the free hormone hypothesis. Here, we demonstrated that megalin imports testosterone bound to sex hormone-binding globulin into prostate cells. Prostatic loss of Lrp2 (megalin) in a mouse model resulted in reduced prostate testosterone and dihydrotestosterone (DHT) levels. Megalin expression was regulated and suppressed by 25-hydroxyvitamin D (25D) in cell lines, patient-derived prostate epithelial cells, and prostate tissue explants, indicating a negative feedback loop. In patent samples, the relationships between hormones support this feedback mechanism, as prostatic DHT levels are higher in African American men and are inversely correlated with serum 25D status. Megalin levels are reduced in localized PCa by the Gleason grade and in patients with future disease recurrence. Our findings suggest that the free hormone hypothesis should be revisited for testosterone and highlight the impact of vitamin D deficiency on prostate androgen levels, which are known drivers of PCa. Thus, we revealed a mechanistic link between vitamin D and PCa disparities observed in African Americans.

cancer biology↗