single cell analysis from prostates from PTEN(i)pe-/- and PTEN/VDR(i)pe-/-
Prostate cancer (PCa)-related deaths highly corelate with its metastatic spread due to limited efficiency of current therapies. In addition, the cases of de novo metastatic hormone-naïve prostate cancer (mHNPC) are increasing, highlighting the urgent need to identify novel biomarkers and treatment strategies for PCa spread. The impact of vitamin D receptor (VDR) signaling on prostate tumorigenesis remains unknown despite several epidemiologic studies suggesting its preventive role. Here, the consequences of VDR loss in prostatic epithelial cells (PECs) are studied using a relevant mouse model of PCa, Pten(i)pe-/- mice. We show that loss of VDR promotes oxidative stress in prostatic neoplasia that in turn enhances PECs proliferation. Moreover, VDR-loss leads to higher CXCL5 secretion by PTEN-deficient PECs, enhancing immunosuppressive neutrophils infiltration in prostates. Additionally, our data highlight elevated circulating neutrophil levels as a biomarker for PTEN-deficient PCa dissemination to the liver, and show the efficiency of targeting neutrophil chemotaxis to limit cancer spread. Overall, this work demonstrates how vitamin D signaling slows down PTEN-loss driven tumorigenesis and suggests new therapeutic and diagnostic strategies for mHNPC. Overall design: 2 samples were analyzed, and prepared from dissociated prostates