Bone matrix osteonectin limits prostate cancer cell growth and survival

► We modeled prostate cancer cell-bone matrix interactions in vitro. ► Osteonectin-null bone matrix was disorganized. ► Osteonectin-null bone matrix promoted prostate cancer cell proliferation. ► Osteonectin-null bone matrix promoted resistance to radiation-induced cell death. ► Osteonectin may suppress prostate cancer pathogenesis in the skeletal microenvironment.