EXTRACELLULAR VESICLES AT THE INTERFACE OF PROSTATE CANCER AND BONE: IMPACT OF IONIZING RADIATION

• Grant number: 25/22800-6
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Pietro Ciancaglini
• Grantee: Iara Souza Lima
• Supervisor: Mebarek Saida
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Université Claude Bernard Lyon 1, France
• Associated to the scholarship: 24/04140-6 - Effects of Ionizing Radiation on Vesicle-Guided Bone Mineralization: Therapeutic Perspectives, BP.PD

Abstract

Prostate cancer (PCa) remains the second leading cause of cancer-related death in men and exhibits a pronounced tropism for bone microenvironment, where metastatic lesions are predominantly osteoblastic and clinically incurable. Increasing evidence indicates that extracellular vesicles (EVs) mediate bidirectional communication between tumor and bone cells, shaping the metastatic progression and bone remodeling of both. Ionizing radiation, a cornerstone of prostate cancer therapy, is classically recognized for inducing DNA damage; however, emerging studies suggest that radiation also alters vesicle biogenesis and cargo, thus reprogramming intercellular signaling. This project investigates how X-ray irradiation modulates the production and function of EVs advanced-stage prostate cancer cells (PC-3) and non-tumorigenic prostate stromal cells (WPMY-1),and how these vesicles influence osteoblast differentiation and mineralization. EVs will be isolated and characterized in terms of morphology, size distribution, molecular composition, and concentration, followed by functional assays in murine pre-osteoblasts (MC3T3-E1 subclone 14) and primary murine calvaria osteoblasts (mOBs). Osteoblast responses will be assessed through viability, alkaline phosphatase activity, calcium deposition, gene expression, and protein analyses. By integrating tumor- and bone-derived vesicular responses to irradiation, this study addresses the central hypothesis that radiation remodels EV-mediated communication between prostate cancer and bone cells, thereby influencing metastatic niche formation, bone integrity, and therapeutic outcome. The interdisciplinarity and collaborative approach, uniting expertise in EV biophysics and mineralization (Brazil) with advanced prostate cancer modeling and radiobiology (France), is expected to provide new mechanistic insights into radiation-modulated tumor-bone interactions and identify potential translational pathways for therapeutic intervention.