Single-Cell Profiling of Bone Metastasis Ecosystems From Multiple Cancer Types Reveals Convergent and Divergent Mechanisms of Bone Colonization

Authors

Fengshuo Liu
Yunfeng Ding
Zhan Xu
Xiaoxin Hao
Tianhong Pan
George Miles
Siyue Wang
Yi-Hsuan Wu
Jun Liu
Igor L Bado
Weijie Zhang
Ling Wu
Yang Gao
Liqun Yu
David G Edwards
Hilda L Chan
Sergio Aguirre
Michael Warren Dieffenbach
Elina Chen
Yichao Shen
Dane Hoffman
Luis Becerra Dominguez
Charlotte Helena Rivas
Xiang Chen
Hai Wang
Zbigniew Gugala
Robert L Satcher
Xiang H-F Zhang

Language

English

Publication Date

7-9-2025

Journal

Cell Genomics

DOI

10.1016/j.xgen.2025.100888

PMID

40412393

PMCID

PMC12278635

PubMedCentral® Posted Date

5-23-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Bone Neoplasms, Humans, Single-Cell Analysis, Osteoclasts, Neoplasms, Macrophages, Tumor Microenvironment, bone metastases, single-cell RNA sequencing, tumor microenvironment, immune archetypes, immunosuppression, immune evasion, convergent and divergent evolution

Published Open-Access

yes

Recommended Citation

Liu, Fengshuo; Ding, Yunfeng; Xu, Zhan; et al., "Single-Cell Profiling of Bone Metastasis Ecosystems From Multiple Cancer Types Reveals Convergent and Divergent Mechanisms of Bone Colonization" (2025). Faculty and Staff Publications. 4908.
https://digitalcommons.library.tmc.edu/baylor_docs/4908