Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

Holzapfel, Boris M., Wagner, Ferdinand, Loessner, Daniela, Holzapfel, Nina P., Thibaudeau, Laure, Crawford, Ross, Ling, Ming-Tat, Clements, Judith A., Russell, Pamela J., & Hutmacher, Dietmar W. (2014) Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone. Biomaterials, 35(13), pp. 4108-4115.

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Abstract

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

Impact and interest:

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22 citations in Web of Science®

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ID Code: 68126
Item Type: Journal Article
Refereed: Yes
Keywords: Bone metastasis, Prostate Cancer, Homing, Tissue Engineering, Humanized bone, Osteotropism
DOI: 10.1016/j.biomaterials.2014.01.062
ISSN: 0142-9612
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 06 Mar 2014 04:55
Last Modified: 26 Aug 2014 21:55

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