Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts

Ali Shokoohmand; Jiongyu Ren; Jeremy Baldwin; Anthony Atack; Abbas Shafiee; Christina Theodoropoulos; Marie-Luise Wille; Phong A Tran; Laura J Bray; Deborah Smith; Naven Chetty; Pamela M Pollock; Dietmar W Hutmacher; Judith A Clements; Elizabeth D Williams; Nathalie Bock

doi:10.1016/j.biomaterials.2019.119402

Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts

Biomaterials. 2019 Nov:220:119402. doi: 10.1016/j.biomaterials.2019.119402. Epub 2019 Jul 31.

Authors

Ali Shokoohmand¹, Jiongyu Ren², Jeremy Baldwin², Anthony Atack³, Abbas Shafiee², Christina Theodoropoulos², Marie-Luise Wille², Phong A Tran², Laura J Bray⁴, Deborah Smith⁵, Naven Chetty⁵, Pamela M Pollock⁶, Dietmar W Hutmacher⁷, Judith A Clements⁸, Elizabeth D Williams³, Nathalie Bock⁹

Affiliations

¹ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia.
² Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia.
³ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia.
⁴ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia.
⁵ Cancer Pathology Research Group, Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia; Department of Anatomical Pathology, Mater Hospital Brisbane, QLD, Australia.
⁶ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia.
⁷ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, QUT, Kelvin Grove, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia.
⁸ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, QUT, Kelvin Grove, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia.
⁹ Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, QLD, Australia; Australian Prostate Cancer Research Centre, Queensland (APCRC-Q), QUT, Brisbane, QLD, Australia; Translational Research Institute (TRI), QUT, Brisbane, QLD, Australia; Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove, QLD, Australia; School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, Australia. Electronic address: n.bock@qut.edu.au.

PMID: 31400612
DOI: 10.1016/j.biomaterials.2019.119402

Abstract

Representative in vitro models that mimic the native bone tumor microenvironment are warranted to support the development of more successful treatments for bone metastases. Here, we have developed a primary cell 3D model consisting of a human osteoblast-derived tissue-engineered construct (hOTEC) indirectly co-cultured with patient-derived prostate cancer xenografts (PDXs), in order to study molecular interactions in a patient-derived microenvironment context. The engineered biomimetic microenvironment had high mineralization and embedded osteocytes, and supported a high degree of cancer cell osteomimicry at the gene, protein and mineralization levels when co-cultured with prostate cancer PDXs from a lymph node metastasis (LuCaP35) and bone metastasis (BM18) from patients with primary prostate cancer. This fully patient-derived model is a promising tool for the assessment of new molecular mechanisms and as a personalized pre-clinical platform for therapy testing for patients with prostate cancer bone metastases.

Keywords: Bone metastasis; Cancer model; Osteocyte; Osteomimicry; Patient-derived xenograft; Prostate cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Biomimetics*
Bone Matrix / metabolism
Bone Neoplasms / genetics
Bone Neoplasms / secondary*
Bone and Bones / pathology
Bone and Bones / ultrastructure
Calcification, Physiologic
Cell Line, Tumor
Cell Movement
Cell Survival
Extracellular Matrix / metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice, Inbred NOD
Osteoblasts / pathology*
Osteocytes / metabolism
Osteocytes / ultrastructure
Prostatic Neoplasms / pathology*
Tissue Engineering*
Tissue Scaffolds / chemistry
Tumor Microenvironment*
Xenograft Model Antitumor Assays*