A team from Lawson Health Research Institute has shown that triple-negative breast cancer cells can facilitate changes to the lung that both attract cancerous cells and allow them to grow, leading to lung metastasis.
Metastasis is the spread of cancer cells from a primary tumour to different organs. Lung metastasis is responsible for approximately 60 to 70 per cent of deaths related to breast cancer.
“The best way to explain lung metastasis is the seed and soil analogy,” says Dr. Alison Allan, Lawson Scientist. “The seeds are the breast cancer cells from a primary tumour and the soil is the lung’s microenvironment. Seeds can break away, but they only grow if the soil is fertile.”
The majority of studies on metastatic cancer have focused on the characteristics of tumour cells and not on the organs to which they spread. Dr. Allan’s team is studying how the lung microenvironment itself is contributing to lung metastasis.
In the new study, the team examined the lung microenvironment in preclinical models. They compared models with two different subtypes of breast cancer. The luminal A subtype is the least aggressive form of breast cancer and does not often metastasize to the lung. Triple-negative breast cancer, meanwhile, is the most aggressive form with a higher likelihood of metastasis and no targeted therapies available.
The team found that models with triple-negative breast cancer had a drastically different lung microenvironment that was much more hospitable to the growth of cancer. They also found that triple-negative breast cancer cells might be sending ‘signals’ to the lung to help it attract cancerous cells that enter the bloodstream.
“We suspect that triple-negative breast cancer cells release tiny particles called exosomes which are delivered to the lung,” explains Dr. Allan, who is also Chair of the Department of Anatomy and Cell Biology at Western University’s Schulich School of Medicine & Dentistry. “Once delivered, the exosomes signal the lung to start changing into a hospitable environment for tumour cells.”
With support from Lawson’s Internal Research Fund, the team is continuing to research this process. They are also studying ways to make the lungs less receptive to cancerous cells.
Their findings could help in the development of targeted therapies to prevent breast cancer from metastasizing. For example, in collaboration with investigators at the University of Alberta, they are developing an inhalable spray that is aimed at preventing cancer from spreading to and growing in healthy lungs.
“The ultimate goal is to eliminate the metastasis-promoting exosomes as a therapeutic strategy to prevent triple-negative breast cancer from spreading to the lungs,” says Dr. Allan.
The study “Triple-Negative Primary Breast Tumours Induce Supportive Premetastatic Changes in the Extracellular Matrix and Soluble Components of the Lung Microenvironment,” is published in Cancers. It was funded by the Cancer Research Society, the Canadian Cancer Society Research Institute, a London Regional Cancer Program Catalyst Grant, London Health Sciences Foundation, the Breast Cancer Society of Canada and an Ontario Graduate Scholarship awarded to Braeden Medeiros – the paper’s first author.
Above: Visual representation of the research findings
