@article{db6245d87d9e4090bbd5fdc13e033af4,
title = "Bone metastasis initiation is coupled with bone remodeling through osteogenic differentiation of NG2+ cells",
abstract = "The bone microenvironment is dynamic and undergoes remodeling in normal and pathologic conditions. Whether such remodeling affects disseminated tumor cells (DTC) and bone metastasis remains poorly understood. Here, we demonstrated that pathologic fractures increase metastatic colonization around the injury. NG2 + cells are a common participant in bone metastasis initiation and bone remodeling in both homeostatic and fractured conditions. NG2 + bone mesenchymal stem/stromal cells (BMSC) often colocalize with DTCs in the perivascular niche. Both DTCs and NG2 + BMSCs are recruited to remodeling sites. Ablation of NG2 + lineage impaired bone remodeling and concurrently diminished metastatic colonization. In cocultures, NG2 + BMSCs, especially when undergoing osteodifferentiation, enhanced cancer cell proliferation and migration. Knockout of N-cadherin in NG2 + cells abolished these effects in vitro and phenocopied NG2 + lineage depletion in vivo. These findings uncover dual roles of NG2 + cells in metastasis and remodeling and indicate that osteodifferentiation of BMSCs promotes metastasis initiation via N-cadherin–mediated cell–cell interaction.",
keywords = "Bone Neoplasms/genetics, Bone Remodeling, Cadherins/genetics, Cell Differentiation, Humans, Neoplasm Recurrence, Local, Osteogenesis/genetics, Tumor Microenvironment",
author = "Weijie Zhang and Zhan Xu and Xiaoxin Hao and Tiancheng He and Jiasong Li and Yichao Shen and Kai Liu and Yang Gao and Jun Liu and Edwards, {David G.} and Muscarella, {Aaron M.} and Ling Wu and Liqun Yu and Longyong Xu and Xi Chen and Wu, {Yi Hsuan} and Bado, {Igor L.} and Yunfeng Ding and Sergio Aguirre and Hai Wang and Zbigniew Gugala and Satcher, {Robert L.} and Wong, {Stephen T.C.} and Zhang, {Xiang H.F.}",
note = "Funding Information: We are grateful to the discussion and suggestions from the Zhang laboratory members. We also thank Dr. Dongsu Park (Baylor College of Medicine) and Dr. Yangjin Bae (Baylor College of Medicine) for providing relevant animal strains. X.H.-F. Zhang is supported by the U.S. Department of Defense DAMD W81XWH-16-1-0073 (Era of Hope Scholarship), NCI CA183878, NCI CA251950, DAMD W81XWH-20–1-0375, the Breast Cancer Research Foundation, and the McNair Medical Institute. S.T.C. Wong and J. Li are supported in part by NCI U01CA252553, the John S. Dunn Research Foundation, and the T.T. and W.F. Chao Center for BRAIN. Y. Gao received training support from the Translational Breast Cancer Research Training Program (NIH T32 CA203690, principal investigator: Suzanne Fuqua). This project was supported by the RNA In Situ Hybridization Core with funding from the NIH (1S10OD016167), the Cytometry and Cell Sorting Core with funding from the Cancer Prevention & Research Institute of Texas (CPRIT) Core Facility Support Award (CPRIT-RP180672), the NIH (P30 CA125123, S10 RR024574, and S10 OD025251), the Pathology Core of Lester and Sue Smith Breast Center, the Optical Imaging and Vital Microscopy Core and the Integrated Microscopy Core at Baylor College of Medicine, and the MD Anderson Cancer Center Research Histology Core and Bone Histomorphometry Core Laboratory. We also acknowledge Dr. Cecilia Ljungberg, Joy Guo, Rena Mao, and Joel M. Sederstrom at the Baylor College of Medicine and Leah Guerra at MD Anderson Cancer Center for their expert assistance. Publisher Copyright: {\textcopyright} 2023, American Association for Cancer Research Inc.. All rights reserved.",
year = "2023",
month = feb,
day = "1",
doi = "10.1158/2159-8290.CD-22-0220",
language = "English (US)",
volume = "13",
pages = "474--495",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "2",
}