Metastatic tumours originating from notoriously aggressive triple-negative breast cancer that emerge in the lungs contain a more diverse array of cancer cells than those that arise in the liver, according to a new study in mice and organs from deceased cancer patients.
The study also identified a set of genes that distinguish lung and liver metastases; together, the findings may inform future research on how targeted therapies impact tumours across various microenvironments.
While scientists have known that the presence of distinct tumour cell populations within the same tumour drives breast cancer progression, it has not been fully understood why this dangerous cellular diversity develops within some tumours and not others.
To investigate how metastases vary based on host tissue type, Jean Berthelet and colleagues optimised a new optical barcoding strategy and analysed 31 triple-negative breast cancer subclones (subpopulations of cells descended from cancer cells).
The researchers injected fluorescently labeled cells into the mammary fat pads of mice with cancer and mapped the clonal composition of thousands of metastases in the lungs and liver, where triple-negative breast cancer cells tend to spread.
They found that the inflammatory tumour necrosis factor alpha (TNF-? ) pathway was particularly upregulated in metastases in the lungs compared with those in the liver, with some genes in this pathway potentially responsible for the success of lung metastases.
Berthelet et al. also collected 4 lung and 7 liver metastases from autopsies of 3 patients with breast cancer, confirming that the genes they identified were also expressed differently between the lungs and liver in humans.