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Engineered bone for probing organotypic growth and therapy response of prostate cancer tumoroids in vitro.

ABSTRACT: Mechanistic analysis of metastatic prostate cancer (PCa) biology and therapy response critically depends upon clinically relevant three-dimensional (3D) bone-like, organotypic culture. We here combine an engineered bone-mimetic environment (BME) with longitudinal microscopy to test the growth and therapy response of 3D PCa tumoroids. Besides promoting both tumor-cell autonomous and microenvironment-dependent growth in PCa cell lines and patient-derived xenograft cells, the BME enables in vivo-like tumor cell response to therapy, and reveals bone stroma dependent resistance to chemotherapy and BME-targeted localization and induction of cytoxicity by Radium-223. The BME platform will allow the propagation, compound screening and mechanistic dissection of patient-derived bone tumor isolates and applications toward personalized medicine.

SUBMITTER: Paindelli C

PROVIDER: S-EPMC7094882 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Engineered bone for probing organotypic growth and therapy response of prostate cancer tumoroids in vitro.

Paindelli Claudia C Navone Nora N Logothetis Christopher J CJ Friedl Peter P Dondossola Eleonora E

Biomaterials 20190121

Mechanistic analysis of metastatic prostate cancer (PCa) biology and therapy response critically depends upon clinically relevant three-dimensional (3D) bone-like, organotypic culture. We here combine an engineered bone-mimetic environment (BME) with longitudinal microscopy to test the growth and therapy response of 3D PCa tumoroids. Besides promoting both tumor-cell autonomous and microenvironment-dependent growth in PCa cell lines and patient-derived xenograft cells, the BME enables in vivo-li ...[more]

PMID: 30682644

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