Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization

Year: 2025

Type: article

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.

Source: Cell Genomics

DOI: 10.1016/j.xgen.2025.100888

Institutions: Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, The University of Texas MD Anderson Cancer Center, The University of Texas at Austin, The University of Texas Medical Branch at Galveston

Language: English

Topic: Cancer Cells and Metastasis

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $8,900

Funders: U.S. Department of Defense, Breast Cancer Research Foundation, Cancer Prevention and Research Institute of Texas, Baylor College of Medicine, National Institutes of Health, U.S. Public Health Service, National Cancer Institute

OpenAlex ID: W4410628816