Bone is a frequent site for metastasis in solid cancers, yet the histological and molecular characteristics of bone metastases remain largely unexplored. A recent study published in Cell Genomics by researchers from Baylor College of Medicine and the University of Texas MD Anderson Cancer Center employs RNA sequencing to examine bone metastases from eight cancer types, identifying 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," stated Dr. Xiang H.-F. Zhang, co-corresponding author and director of the Lester and Sue Smith Breast Center at Baylor.
The research team, including Dr. Robert L. Satcher from MD Anderson, collected 42 samples of bone metastases from eight cancer types. "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," said Satcher.
Through RNA sequencing, researchers identified three distinct ecosystem archetypes enriched with various immune cells: macrophages and osteoclasts; regulatory and exhausted T cells; and monocytes. These archetypes were validated using existing RNA sequencing data from 158 bone metastases across 10 cancer types.
The study revealed that archetype does not always align with tumor origin; metastases from identical cancer types could belong to different archetypes while those from different types could share an archetype. This suggests convergent and divergent evolutionary pathways where cancers may develop similar mechanisms despite differing origins or evolve parallel mechanisms even when originating from the same organ.
"Our analysis identified a large number of potential therapeutic targets within each archetype that can be studied for validation," said Fengshuo Liu, first author and graduate student in the Zhang lab. The data has been made publicly available for further research by other groups.
"This study highlights the power of pan-cancer research," noted Zhang, emphasizing the opportunity to study diverse cancer types within a unified microenvironment in bones.
Contributors to this work include Yunfeng Ding, Zhan Xu, Xiaoxin Hao among others affiliated with Baylor College of Medicine, MD Anderson Cancer Center, and University of Texas Medical Branch.
This research received support from several institutions including the U.S. Department of Defense (W81XWH-21-1-0790), National Cancer Institute (CA183878), Breast Cancer Research Foundation among others.
