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Biomaterials ; 220: 119402, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31400612

RESUMO

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.


Assuntos
Biomimética , Neoplasias Ósseas/secundário , Osteoblastos/patologia , Neoplasias da Próstata/patologia , Engenharia Tecidual , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Idoso , Animais , Matriz Óssea/metabolismo , Neoplasias Ósseas/genética , Osso e Ossos/patologia , Osso e Ossos/ultraestrutura , Calcificação Fisiológica , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos NOD , Osteócitos/metabolismo , Osteócitos/ultraestrutura , Alicerces Teciduais/química
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