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.
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.
Biomaterials. 2019 Nov;220:119402. doi: 10.1016/j.biomaterials.2019.119402. Epub 2019 Jul 31.
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.
需要有代表性的体外模型来模拟天然的骨肿瘤微环境，以支持开发更成功的骨转移治疗方法。在这里，我们开发了一种由人成骨细胞衍生的组织工程构建体（hOTEC）组成的原发性细胞 3D 模型，该模型与患者来源的前列腺癌异种移植物（PDX）间接共培养，以研究在患者来源的微环境背景下的分子相互作用。该工程仿生微环境具有高矿化和嵌入的成骨细胞，并且当与来自原发性前列腺癌的淋巴结转移（LuCaP35）和骨转移（BM18）的前列腺癌 PDX 共培养时，在基因、蛋白质和矿化水平上支持高度的癌细胞成骨模拟。这种完全患者来源的模型是评估新分子机制的有前途的工具，并且是用于测试前列腺癌骨转移患者治疗的个性化临床前平台。
