‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Department of Urology and Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
Author to whom correspondence should be addressed.
Received: 14 December 2020 / Revised: 1 January 2021 / Accepted: 8 January 2021 / Published: 12 January 2021
Patients with late-stage bone metastatic breast cancer experience skeletal related events, including osteolytic lesion formation, due to overactive osteoclast bone resorption. It is well-known that osteoclast function is altered by breast cancer cells in bone. Breast cancer cells stimulate osteoblasts to secrete factors that initiate osteoclast differentiation and activation. Our lab has previously identified a novel subpopulation of osteoblasts in the bone-tumor microenvironment called “educated” osteoblasts (EOs) that alter breast cancer cell proliferation. The aim of this study was to identify how osteoclasts are affected by EOs during metastatic breast cancer progression in bone. Our results demonstrated that pre-osteoclast interaction with EOs reduces osteoclast formation and bone resorption in a bone-tumor mimetic microenvironment. Furthermore, we identified that altered osteoclast formation can be modulated, in part, by tumor necrosis factor alpha (TNFα). Overall, our data demonstrate osteoclastogenesis is reduced by EO cells, suggesting EO cells have a protective effect in bone and exert an inhibitory effect on tumor progression.