Abstract 1165: A tissue-engineered bone mimetic in vitro model for monitoring metastatic PCa growth and therapy response

Abstract

Abstract Despite recent advances in prostate cancer (PCa) treatment, the outcome of metastatic disease remains frequently fatal and the underlying biology poorly understood. Thus, the development of clinically relevant in vitro models to monitor PCa biology in organotypic bone-like environment is critical to uncover mechanisms of therapy resistance and identify more effective treatments. To establish a bone-mimetic culture, we combined the following components: (i) bioactive osteoblasts depositing bone-like calcified extracellular matrix, (ii) complex 3D surface geometries, (iii) multicellular tumor application as spheroids/organoids, and (iv) applicability for live-cell microscopy to monitor the development of lesions over time. Calcified polycaprolactone (PCL) scaffolds were functionalized with bone-derived human mesenchymal stem cells (hMSCs) differentiated to osteoblasts, to generate a 3D niche-like calcified scaffold. PCa spheroids (PC3, C4-2B, patient-derived xenografts) were on-planted and their growth and invasion longitudinally monitored by advanced microscopy. PCa spheroids seeded on the organotypic bone model could be maintained and expanded over weeks, sufficient for monitoring therapy response to docetaxel, a first-line therapy for advanced PCa. The bone mimetic culture further revealed resistance to docetaxel mainly at the invasive edges, through a mechanism depending on the presence of osteoblasts. Thus, this 3D in vitro organotypic model will be suitable for dissecting the physical and molecular PCa cell-osteoblast interaction involved in PCa growth and therapy resistance. Citation Format: Claudia Paindelli, Dietmar Hutmacher, Peter Friedl, Eleonora Dondossola. A tissue-engineered bone mimetic in vitro model for monitoring metastatic PCa growth and therapy response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1165.