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

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Shokoohmand, A
Ren, J
Baldwin, J
Atack, A
Shafiee, A
Theodoropoulos, C
Wille, ML
Tran, PA
Bray, LJ
Smith, D
Chetty, N
Pollock, PM
Hutmacher, DW
Clements, JA
Williams, ED
Bock, N
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2019
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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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Biomaterials

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220

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Nanotechnology

Science & Technology

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Engineering, Biomedical

Materials Science, Biomaterials

Engineering

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Shokoohmand, A; Ren, J; Baldwin, J; Atack, A; Shafiee, A; Theodoropoulos, C; Wille, ML; Tran, PA; Bray, LJ; Smith, D; Chetty, N; Pollock, PM; Hutmacher, DW; Clements, JA; Williams, ED; Bock, N, Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts, Biomaterials, 2019, 220, pp. 119402: 1-119402: 17

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