Abstract
Abstract Bone metastases are a major complication in patients with advanced prostate cancer (PCa) and frequent cause of therapy resistance. Besides cell intrinsic mechanisms, signals received from the bone microenvironment critically contribute to support PCa cell survival and growth. Recent advances in intravital microscopy enable to investigate this complex PCa cell-microenvironment interaction and allow preclinical examination of tumor responses to both conventional and targeted therapy. We developed a window model amenable to intravital multiphoton microscopy (MPM) to longitudinally monitor PCa lesions in humanized neobone established in the dermis of the mouse. Tissue engineered bone constructs, TEBCs, were generated by functionalizing polymeric polycaprolactone scaffolds with human mesenchymal stem cells differentiated to osteoblasts, and characterized in vitro for cell distribution and calcium deposition. After in vivo implantation, TEBC maturation was monitored by μCT, MPM and histological analysis over time to generate a miniaturized-neobone with defined cortical thickness (50-60 μm) suitable for intravital imaging through a body window. PCa (PC3) lesions, after implantation into the bone cavity, were longitudinally monitored for growth and niche development, using multi-parameter recording of: collagen/bone matrix (SHG), bone surface (THG), blood vessels/stromal phagocytes (fluorescent dextran), and PC3 cells (nuclear H2BeGFP, cytoplasmatic DsRed2). By combining innovative tissue engineering with optical windows, state-of-the-art fluorescence reporter technology and intravital MPM, this model will provide mechanistic and applied insight into the therapy response of bone metastasis. Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris Holzapfel, Christopher Logothetis, Dietmar Hutmacher, Peter Friedl. Preclinical monitoring of prostate cancer lesions in bone by intravital multiphoton microscopy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5175. doi:10.1158/1538-7445.AM2015-5175
Published Version
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