The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile
- Author(s)
- Berthelet, J; Wimmer, VC; Whitfield, HJ; Serrano, A; Boudier, T; Mangiola, S; Merdas, M; El-Saafin, F; Baloyan, D; Wilcox, J; Wilcox, S; Parslow, AC; Papenfuss, AT; Yeo, B; Ernst, M; Pal, B; Anderson, RL; Davis, MJ; Rogers, KL; Hollande, F; Merino, D;
- Details
- Publication Year 2021-07,Volume 7,Issue #28,Page eabf4408
- Journal Title
- Science Advances
- Publication Type
- Research article
- Abstract
- Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor-alpha pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.
- Keywords
- *Breast Neoplasms/genetics/pathology; Female; Humans; *Liver Neoplasms/genetics/pathology; *Lung Neoplasms/pathology; Neoplasm Metastasis; Transcriptome; Tumor Microenvironment/genetics
- Department(s)
- Laboratory Research
- PubMed ID
- 34233875
- Publisher's Version
- https://doi.org/10.1126/sciadv.abf4408
- Open Access at Publisher's Site
https://doi.org/10.1126/sciadv.abf4408- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-06-06 07:51:47
Last Modified: 2025-06-06 07:57:04