Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium

摘要

a FVB mice pre-fed low-fat or high-fat diet to induce DIO were grafted with HMVP2 spheroids. Representative resected tumors were analyzed for CXCL12 and E-Cadherin (arrows) in tumor sections. Note membrane E-cadherin (inset: high magnification) and its loss (indicating EMT) concomitant with CXCL12 expression in DIO. b IF on sections of ventral prostates of 6-month-old HiMyc mice fed chow (control) or HFD (obese) reveals proliferation (Ki67+) in tumor cells lacking E-cadherin in obesity. Quantification of IF data (based on counts from N = 5 view fields) from mice raised on chow and HFD is graphed on the right. c IF on sections of ventral prostates of control and obese HiMyc mice (9 months old). E-cadherin in prostate epithelium (arrow) is downregulated in DIO mice concomitantly with fibronectin induction in the stroma (arrowhead). d HiMyc mice maintained on HFD treated with D-CAN starting at 12 weeks of age for 4 weeks and terminated at 16 (experiment 1) or 24 (experiment 2) weeks of age have lower urinary tract weight, compared to control mice treated with PBS. N = 5. e IF analysis of ventral prostate of mice from d. Note induction of E-cadherin in epithelium concomitant with reduction of CXCL12 in the stroma, indicating EMT reversal upon D-CAN treatment. Graph: quantification of CXCL12+ cells in the stroma in (e); N = 5. For all panels, *P < 0.05 compared to control (Student’s t test). Scale bar = 100 µm.