Identification of Genes Regulating Breast Cancer Dormancy in 3D Bone Endosteal Niche Cultures.

ABSTRACT: Tumor cell dormancy is a significant clinical problem in breast cancer. We used a three-dimensional (3D) in vitro model of the endosteal bone niche (EN), consisting of endothelial, bone marrow stromal cells, and fetal osteoblasts in a 3D collagen matrix (GELFOAM), to identify genes required for dormancy. Human triple-negative MDA-MB-231 breast cancer cells, but not the bone-tropic metastatic variant, BoM1833, established dormancy in 3D-EN cultures in a p38-MAPK-dependent manner, whereas both cell types proliferated on two-dimensional (2D) plastic or in 3D collagen alone. "Dormancy-reactivation suppressor genes" (DRSG) were identified using a genomic short hairpin RNA (shRNA) screen in MDA-MB-231 cells for gene knockdowns that induced proliferation in the 3D-EN. DRSG candidates enric

SUBMITTER: McGrath J 

PROVIDER: S-EPMC6445695 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature