Interaction between killer macrophages and prostatic epithelial cells: analyses of oxidative stress in 3D cultures

• Grant number: 25/26230-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Letícia Maria Ruiz Trevisan
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/02303-7 - Single cell analyses and non-linear optics approaches of prostate biology, AP.TEM

Abstract

Androgens are important for the development and homeostasis of the prostate gland. After 3 days of androgen deprivation, a peak of prostatic epithelial cell apoptosis occurs, along with an influx of immune cells, including M1142 macrophages. These macrophages are iNOS-positive and carry the znf142 and CX3CR1 genes. Studies have shown that RAW 264.7 macrophages stimulated by LNCAP conditioned medium attack LNCAP prostate tumor cells in the absence of androgen, via the intrinsic pathway of apoptosis. Our recent findings demonstrate that a progranulin peptide fragment (designated Pep A) released by prostate epithelial cells is responsible for reprogramming macrophages into killer cells. Therefore, this project aims to identify apoptosis in 3D co-cultured spheroids using TUNEL and immunofluorescence in the presence of peptide A, as well as in 2D co-cultures using time-lapse staining with a cell tracker and the detection of oxidative stress using the H2DCFDA probe. Ultimately, this project may provide new insights into clinical therapy for castration-resistant prostate cancer. (AU)