Graphical summary Credit score: Cell Genomics (2025). DOI: 10.1016/j.xgen.2025.100888
Bone is a standard website for metastasis of stable cancers, however histological and molecular options of bone metastases should not effectively understood. In a brand new research revealed in Cell Genomics, researchers at Baylor Faculty of Medication and the College of Texas MD Anderson Most cancers Heart use RNA sequencing to characterize bone metastases from eight most cancers sorts. The findings establish three distinct immune ecosystem archetypes.
“Bone metastases vary widely from person to person, yet all bone metastases are treated similarly with treatment targeting one cell type, osteoclasts. Some patients do not respond to this treatment. In this study, we examined the heterogeneity of bone metastases across different cancer types and within each cancer type,” mentioned co-corresponding creator Dr. Xiang H.-F. Zhang, director of the Lester and Sue Smith Breast Heart and professor of molecular and mobile biology at Baylor.
The Zhang lab labored with Dr. Robert L. Satcher, an orthopedic surgeon and affiliate professor within the Division of Orthopaedic Oncology at MD Anderson, to acquire 42 bone metastases samples from eight completely different most cancers sorts.
“The interesting finding is that there are both similarities and differences that are cancer-type specific. Dr. Zhang’s work previously focused on breast cancer bone metastasis, and I focused on renal cell carcinoma bone metastasis. By working together, we were able to approach the problem with a unique combined perspective, which critically informed our research strategy,” mentioned Satcher, co-corresponding creator of the research.
Immunofluorescence staining verifies distinct immune archetypes. Credit score: Cell Genomics (2025). DOI: 10.1016/j.xgen.2025.100888
Researchers carried out RNA sequencing and located the metastases fell into three distinct ecosystem archetypes characterised by enrichment of various immune cells: macrophages and osteoclasts, regulatory and exhausted T cells, and monocytes. They validated the archetypes utilizing beforehand revealed RNA sequencing knowledge of 158 bone metastases throughout 10 most cancers sorts.
The group discovered that archetype doesn’t all the time coincide with tumor origin. Metastases from the identical most cancers kind usually fell into completely different archetypes, and metastases from completely different most cancers sorts generally fell into the identical archetype. These findings point out each convergent and divergent evolution pathways—cancers originating from completely different organs can evolve related immunosuppression and bone colonization mechanisms, and cancers from the identical main organ can develop parallel mechanisms.
The outcomes of this research counsel a necessity to analyze completely different remedy methods for various archetypes. For instance, metastases within the exhausted T cell archetype might reply higher to interventions that activate these T cells, reasonably than conventional anti-osteoclast remedy.
“Our analysis identified a large number of potential therapeutic targets within each archetype that can be studied for validation,” mentioned first creator Fengshuo Liu, graduate scholar within the Zhang lab. “Our data is all publicly available, and many groups are already using it for other studies.”
“This study highlights the power of pan-cancer research. The border of different cancer types becomes blurred when they all come to the same place in the bone, so this is a unique opportunity to study different types in the same microenvironment,” mentioned Zhang, William T. Butler, M.D., Endowed Chair for Distinguished College and co-leader of the Breast Most cancers Program on the Dan L Duncan Complete Most cancers Heart at Baylor.
Extra data:
Fengshuo Liu et al, Single-cell profiling of bone metastasis ecosystems from a number of most cancers sorts reveals convergent and divergent mechanisms of bone colonization, Cell Genomics (2025). DOI: 10.1016/j.xgen.2025.100888
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Baylor Faculty of Medication
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Single-cell RNA sequencing of bone metastases from a number of most cancers sorts reveals three distinct immune archetypes (2025, Could 23)
retrieved 24 Could 2025
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