Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patient-derived prostate cancer xenografts.
Biomaterials
; 220: 119402, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31400612
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Neoplasias da Próstata
/
Neoplasias Ósseas
/
Ensaios Antitumorais Modelo de Xenoenxerto
/
Engenharia Tecidual
/
Biomimética
/
Microambiente Tumoral
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article