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Engineering osteoblastic metastases to delineate the adaptive response of androgen-deprived prostate cancer in the bone metastatic microenvironment.


ABSTRACT: While stromal interactions are essential in cancer adaptation to hormonal therapies, the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood. Here, we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases, and used it to study the effects of androgen deprivation in this microenvironment. The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds, leading to a mineralized osteoblast-derived microtissue containing, in a 3D setting, viable osteoblastic cells, osteocytic cells, and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins, and mineral content. Direct co-culture of androgen receptor-dependent/independent cell lines (LNCa

SUBMITTER: Bock N 

PROVIDER: S-EPMC6486620 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature