ArticleCell genomics2025
Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization.
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Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed.
- NF1 loss in estrogen receptor-positive breast cancer induces osteoclast formation and immunosuppression to promote bone metastasis.Cancer letters · 2026Article
- ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis Through Symbiotic Adhesion and Reverse Migration.Cancer research · 2026Article
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Hierarchical Targeting of TREM2Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Decoding the Role of MDSCs in Bone Metastasis: Multicellular Interactions and Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A pan-cancer single-cell transcriptomic atlas of human bone metastases.Cell reports. Medicine · 2026Article
- Engineered bone matrix models for understanding breast cancer skeletal metastasis.Cancer metastasis reviews · 2026Review
- Mitochondrial transfer-mediated metabolic reprogramming and drug resistance in bone metastasis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Tumor-associated osteoclasts converge on a matrix-sulfation program across human bone tumors.Frontiers in cell and developmental biology · 2026Article
- Analysis of the heterogeneity of the immune microenvironment of bone metastases and new strategies of nanotechnology intervention.Oncology reviews · 2026Review
- Oxidative Stress Footprints in Bone Marrow Mesenchymal Stem Cells from Untreated Advanced Breast Cancer.Oncology research · 2026Article
- Endogenous Osteocyte-Osteoclast Signaling Enables Growth Factor-Free Bone Remodeling, Drug Response, and Cancer Invasion in a Nanoscale Calcified Bone-on-a-Chip Model.bioRxiv : the preprint server for biology · 2025Article
- Article
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
- Paradigms, innovations, and biological applications of RNA velocity: a comprehensive review.Briefings in bioinformatics · 2025Review
- Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression.PLoS biology · 2025Review
- Decoding metastatic microenvironments through single-cell omics reveals new insights into niche dynamics and tumor evolution.PLoS biology · 2025Article
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Authors and funding
28 authors.
Fengshuo LiuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yunfeng DingLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Zhan XuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xiaoxin HaoLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Tianhong PanDepartment of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
George MilesLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Siyue WangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yi-Hsuan WuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jun LiuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Igor L BadoLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Weijie ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Ling WuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Yang GaoLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Liqun YuLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
David G EdwardsLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hilda L ChanLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Sergio AguirreLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Michael Warren DieffenbachLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, One Baylor Plaza, Houston TX 77030, USA.
Elina ChenCollege of Natural Sciences, University of Texas at Austin, 110 Inner Campus Drive, Austin, TX 78706, USA.
Yichao ShenLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dane HoffmanLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Luis Becerra DominguezLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Charlotte Helena RivasLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xiang ChenLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hai WangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Zbigniew GugalaDepartment of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch, Galveston, TX, USA.
Robert L SatcherDepartment of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: rlsatcher@mdanderson.org.
Xiang H-F ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; McNair Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: xiangz@bcm.edu.
Funding
Osteoclast-Independent Mechanisms of Early-Stage Bone Colonization of Breast CancerR01CA183878 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2014 to 2024
$3.5MNext Generation Rat Models of ER+ Breast CancerR01CA271498 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Yi Li, Xiang Zhang · 2022 to 2026
$3.1MSpatiotemporal modeling of cancer-niche interactions in breast cancer bone metastasisU01CA253553 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHANG, XIANG · 2020 to 2024
$3.0MUnveiling the mechanisms underlying secondary metastasis and possible therapeutic windowsR01CA251950 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2020 to 2024
$2.6MOsteogenic Niche Biology in Progression and Endocrine Resistance of Bone MetastasesR01CA221946 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ROWLEY, DAVID R · 2018 to 2022
$2.4MHigh Memory High-Performance Computer Cluster for Biomedical ResearchS10OD032185 · OD · BAYLOR COLLEGE OF MEDICINE · PI HILSENBECK, SUSAN G. · 2022 to 2022
$596kHarnessing neutrophils to improve the efficacy of immune checkpoint inhibitors in breast cancerR00CA279899 · NCI · OHIO STATE UNIVERSITY · PI Yang Gao · 2025 to 2026
$497kHarnessing neutrophils to improve the efficacy of immune checkpoint inhibitors in breast cancerK99CA279899 · NCI · BAYLOR COLLEGE OF MEDICINE · PI GAO, YANG · 2023 to 2024
$238kNCI NIH HHS K99 CA279899NCI NIH HHS R00 CA279899NCI NIH HHS R01 CA183878NCI NIH HHS R01 CA221946NCI NIH HHS R01 CA251950NCI NIH HHS R01 CA271498NCI NIH HHS U01 CA253553NIH HHS S10 OD032185
Abstract
Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs from the same cancer type often fell into different archetypes, while BMs from different cancer types sometimes converged on the same archetype. Additional analyses revealed parallel immunosuppression and bone remodeling mechanisms, some of which were experimentally validated. Overall, we discovered unappreciated heterogeneity of BMs across different cancers.
Indexed as
Bone NeoplasmsNeoplasmsSingle-Cell AnalysisHumansMacrophagesOsteoclastsTumor Microenvironmentbone metastasesconvergent and divergent evolutionimmune archetypesimmune evasionimmunosuppressionsingle-cell RNA sequencingtumor microenvironment
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