Mechanisms that underlie the early dissemination of tumour cells during breast cancer are described in two papers published online in Nature this week. Both studies show that early disseminated cancer cells (eDCCs) are capable of colonizing distant tissues more efficiently than cells that leave the tumour at later stages. The findings may aid the development of potential new therapies that target eDCCs and prevent metastasis.
Metastasis is the leading cause of cancer-related deaths, and although previous studies have indicated that metastatic dissemination often takes place during the early stages of tumour formation, the underlying mechanisms remain poorly understood.
Christoph Klein and colleagues studied metastasis in a mouse model of HER2-positive breast cancer. They found that cells that migrated early from low-density lesions migrated more and formed more metastases than cells originating from dense, advanced tumours. Notably, at least 80% of metastases were derived from eDCCs. The authors show that the hormone progesterone has a role in triggering the migration of cancer cells from early lesions, while promoting proliferation in advanced primary tumour cells.
In a separate paper, Julio Aguirre-Ghiso and colleagues show that in early breast cancer lesions, before any overt primary tumour masses are detectable, a population of invasive HER2-positive early cancer cells exist that later disseminate to target organs. The authors identify a role for the protein HER2, which activates a signalling pathway that generates eDCCs that are capable of forming a metastasis after a period of dormancy.
In an accompanying News & Views article, Cyrus Ghajar and Mina Bissell note that the mechanisms identified in these studies might not apply across all breast-cancer subtypes or to other cancers. However, they conclude that the findings “provide a general framework within which to study causality between early DCCs and metastasis - particularly for cancers in which early dissemination is a documented phenomenon, such as skin and pancreatic cancers.”