Blocking fat production in lung cells could slow breast cancer metastasis 

Two studies published recently in Nature Cell Biology and Cancer Discovery show that breast cancer cells that have spread to the lungs rely on fats produced by healthy lung cells to grow. They found these fats help breast cancer cells survive and grow in the lungs. 

This research was led by Professor Sarah-Maria Fendt at the VIB-Flemish Institute for Biotechnology (VIB) and funded by Wereld Kanker Onderzoek Fonds (WKOF), which is part of our global network of charities including World Cancer Research Fund and the American Institute for Cancer Research. 

Collaborating with researchers at The Francis Crick Institute in the UK, an international team of scientists identified how breast cancer cells grow after spreading to the lungs, revealing that tumour cells can hijack healthy lung cells and hyperactivate their fat production to help them grow.  

The team also revealed more about how these fats are used to maintain tumour growth and discovered that blocking fat production in lung cells can slow the growth of metastases, pointing to a potential new target for treatment. 

Reprogramming healthy cells makes cancer grow 

Cancer that spreads from the primary tumour to other parts of the body is known as metastatic cancer. Metastasis is the leading cause of cancer deaths and remains a major challengefor cancer care as there are often limited treatment options once cancer has spread. 

The lungs are a common secondary site for cancer cells to spread to, including for breast cancer.  

For metastasis to happen, we know that specific conditions are required to accommodate cancer cells.  Alveolar type II (AT2) cells are specialised lung cells that produce the chemical compound – known as a surfactant – needed to keep the lungs functioning properly and can also help repair lung tissue. Previous work from Prof Fendt’s team have shown that AT2 change before cancer cells arrive to the lung in response to signals from the primary tumour. 

However, the role these lung cells play once metastases have become established in the lung is not yet understood. 

By investigating metastatic cancer in mice and human samples, and employing a range of different laboratory techniques (including mass spectrometry imaging), the team discovered that in the vicinity of metastases, AT2 cells are reprogrammed by the cancer into lipid feeder cells. 

Importantly, the researchers found that metastasis growth was slowed by targeting lipid metabolism in the lung environment rather than in the cancer cells themselves. When they blocked the production of specific fats in AT2 cells with breast cancer that had spread to the lungs, they saw reduced tumour growth. Significantly, this happened without major detectable effects on healthy lung tissue in these experimental models, which functioned the same as healthy cells adapted to the loss of specific fats while cancer cells hadn’t. 

Head of Research Funding at World Cancer Research Fund, Dr Julia Panina, who worked on this paper while completing her PhD at the Francis Crick Institute, says: 

“Through this research, we were able to uncover a new way that metastatic cancer cells exploit the metabolism of the tissues they spread to, to support their survival and growth. These findings could help identify new approaches for preventing and treating metastatic disease in the future.”  

How are these lipids used? 

In a second study, Professor Fendt’s team focused on understanding exactly how cancer cells use these fats once they reach the lungs.  

These specific fats which contained the fatty acid palmitate are known as energy-rich molecules and have long been thought to mainly serve as an energy source for cancer. However,the research team found that cancer cells also use these fats in a different way – to modify proteins and control how they function in the cell. 

These palmitate modifications allow cancer cells to alter their molecular makeup and help them adapt to the lung environment and grow more effectively. 

“So those lipids are not just fuel for cancer cells,” explains Prof. Sarah-Maria Fendt. “They also initiate molecular processes that help the tumour grow. If we interrupt that process, we can block the growth of metastases.” 

Paving the way for new treatments 

These findings help explain how tumours adapt to new environments in the body and has opened the door for further research that could explore new treatment options.  

Encouragingly, reducing fat production significantly slowed the growth of lung metastases in experimental models. This means that rather than targeting cancer cells directly, it also be possible to target other cells that boost their growth. 

“This work highlights the importance of supporting mechanistic research to better understand the biological processes of cancer progression, which is central to the research supported across the WCRF network,” says Dr Panina.