A new study has shed coloured light on how an aggressive breast cancer spreads to vital organs, and on potential genetic targets and drug treatments.

The study, published in Science Advances, used optical barcode technology to ‘paint a picture’ of which Triple Negative Breast Cancer (TNBC) cells spread to lungs and liver in pre-clinical models, and how the cells adapted to and colonised their new homes.

The research found these new homes had a strong impact on different behaviour: the gene expression of the cells had changed from the primary tumour to lung and liver metastases, and this was influenced by neighbouring cells in these tissues.

“Our study revealed that cancer cells have the ability to interact with each other, especially in lung metastases where many different TNBC cells clustered together as multi-coloured groups,” said Dr Jean Berthelet, Postdoctoral Research Fellow in the Tumour Progression and Heterogeneity (TPH) Laboratory at the Olivia Newton-John Cancer Research Institute and La Trobe University’s School of Cancer Medicine.

Dr Berthelet and TPH Laboratory Head Dr Delphine Merino led the study in collaboration with Dr Verena Wimmer and Dr Kelly Rogers from the Walter and Eliza Hall Institute, and Professor Frederic Hollande from the University of Melbourne.

The researchers successfully killed lung and liver metastatic cells with a drug that induces cell death. They also found that a drug used for the treatment of auto-immune diseases could break up the cancer-cell groups in the lungs. Reducing the diversity and communication within groups of cancer cells may enable future treatment strategies, including combined drug treatments.

Breast cancer tumours are composed of cells that are genetically different from each other. Some cells have the ability to spread and grow in other vital organs, often many years after the primary tumours appear. Darwinian theory may also have a say in which cells are successful. Genetic diversity ensures the survival of the sneakiest, including those cancer cells that can traverse the circulatory system, and evade the immune system and standard treatment.

TNBC patients have a higher risk of cancer relapses, including metastases in the liver, lungs, bones and brain. Treatment is often limited to radiotherapy and chemotherapy.

“One of the biggest challenge in breast cancer research is identifying the different cancer cells in a tumour so we can better predict which patient is likely to experience cancer recurrence and find new treatments,” said Dr Merino. “In this study, we were looking for genes that could be targeted by certain drugs to kill aggressive TNBC cells.”

To identify these genes, researchers used fluorescent proteins derived from jellyfish and sea anemones to tag individual TNBC cells with one of 31 different colours. This strategy, called LeGO, enabled them to track the fate of each cell: its movement, the number of ‘offspring’ it produced and its ability to cluster with one of the other 30 coloured cells in the metastases.

They then used genetic sequencing to examine the genetic difference between the same-coloured cancer cells in the primary tumour, the lung metastases and liver metastases.

“We are very grateful to the patients who donated precious samples to cancer research, and we are hoping that some of these results could be used to find better therapeutic strategies for patients with aggressive breast tumours and metastases,” said Dr Merino.

The Susan G. Komen foundation, Cancer Australia, the Australian National Breast Cancer Foundation, the Love your sister Foundation and Cancer Council Victoria supported this study.

Read the full study here