Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer
Ali Shokoohmand1, Jiongyu Ren2, Jeremy Baldwin2
1Institute 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.
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.
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