Journal
SCIENCE ADVANCES
Volume 7, Issue 28, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf4408
Keywords
-
Categories
Funding
- NBCF [IIRS-19-082]
- Susan G. Komen and Cancer Australia [CCR19606878]
- National Health and Medical Research Council of Australia [1164081]
- Tour de Cure Foundation
- Love Your Sister Foundation
- NBCF
- National Health and Medical Research Council of Australia [1164081] Funding Source: NHMRC
Ask authors/readers for more resources
The study optimized the use of optical barcoding to visualize and characterize cancer subclones, revealing that lung metastases were highly polyclonal while liver metastases were not. The transcriptome of the subclones varied according to their metastatic niche, indicating that the heterogeneity observed in metastases is largely dictated by the tumor microenvironment.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available