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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)296-304
Number of pages9
JournalBiomaterials
Volume197
DOIs
StatePublished - Mar 1 2019

Fingerprint

Prostatic Neoplasms
Bone
Bone and Bones
Growth
Tumors
Therapeutics
Cells
Radium
Cellular Microenvironment
Dissection
Neoplasms
Precision Medicine
Chemotherapy
In Vitro Techniques
Heterografts
Medicine
Microscopy
Microscopic examination
Screening
Drug Therapy

Keywords

  • 3D culture
  • Bone metastasis
  • In vitro engineered bone microenvironment
  • Microscopy
  • Prostate cancer
  • Therapy response

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

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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.",
keywords = "3D culture, Bone metastasis, In vitro engineered bone microenvironment, Microscopy, Prostate cancer, Therapy response",
author = "Claudia Paindelli and Navone, {Nora M} and Logothetis, {Christopher J} and Peter Friedl and Eleonora Dondossola",
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AU - Paindelli, Claudia

AU - Navone, Nora M

AU - Logothetis, Christopher J

AU - Friedl, Peter

AU - Dondossola, Eleonora

PY - 2019/3/1

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N2 - 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.

AB - 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.

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KW - Bone metastasis

KW - In vitro engineered bone microenvironment

KW - Microscopy

KW - Prostate cancer

KW - Therapy response

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