New research reveals that immune cells called neutrophils can help breast cancer cells form tumours when they arrive in the lung. And it could lead to new ways to prevent metastatic breast cancer.
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Professor Leo Carlin and his team at the University of Glasgow discovered that in mice with breast cancer, the neutrophils create a kind of “traffic jam” that keeps breast cancer cells stuck in blood vessels in the lung.
And if we can find a way to break the gridlock, this discovery opens the door to new treatments to stop metastatic breast cancer in the lung.
Neutrophils and the lung
When breast cancer spreads beyond the breast, it becomes metastatic. Treatments can hold it back, but we still don’t have a cure.
In around 30% of people living with metastatic breast cancer, tumours spread to the lung. The lung is a unique organ with lots of narrow blood vessels that allow for oxygen to be taken up into the blood, and lots of immune cells to protect against infection.
One type of immune cell found in high numbers in these blood vessels are neutrophils. Previous research has shown that neutrophils can have different roles, either helping or hindering the growth and survival of cancer cells.
In breast cancer, some studies have shown that they can help cancer cells spread to other organs. So in this study, Leo and his team wanted to find out how neutrophils behave in the lungs before metastatic tumours begin to form.
Stuck in traffic
Leo and his team studied mice that would go on to develop metastatic breast cancer in the lung and looked at their lungs before the tumours formed.
They found that the narrow blood vessels of the lung were packed full of neutrophils moving very slowly, as if they were stuck in rush hour traffic.
But how does this help the formation of tumours? The researchers believe that when breast cancer cells reach these blood vessels, they slow down and get stuck amongst the traffic.
To test this idea, they injected fluorescent beads into the mice to see how well blood was flowing through the blood vessels.
Using high-tech microscopy to examine lung tissue, they found fewer beads meaning there was less blood flow through the blood vessels of the lung.
Leo thinks that breast cancer cells become stuck in this neutrophil traffic jam – letting them set down roots and form metastatic tumours in the lung.
Breaking the gridlock
Seeing what’s happening is one thing, but we need to understand why if we want to find ways to stop it.
Previous research has shown that tumours can produce a protein called G-CSF, which increases the number of neutrophils in the body. And because the researchers had already seen a build-up of neutrophils in the lungs, they suspected that G-CSF might be driving this effect.
To test this, they treated healthy mice with G-CSF and found that the same neutrophil traffic jam appeared in the lungs.
The researchers also found that in mice with breast cancer, a protein found on the surface of neutrophils called β2-integrin was not working properly. When it’s working as it should, this protein sits on top of the neutrophils and helps push them along blood vessel walls quickly.
Leo and his team figured that targeting this β2-integrin protein could hold the key to breaking the gridlock and getting the neutrophils moving again. So, they treated mice with breast cancer with an antibody called M18/2, which triggers β2-integrin to begin working properly again.
When they did this, the traffic cleared and the neutrophils sped up once again. And crucially, this also reduced the formation of metastatic tumours in the lungs of the mice.
The long road ahead
While this work is still at an early stage, it opens up new ways of thinking about how to prevent metastatic breast cancer. And with more research, this could help guide future strategies to reduce the risk of cancer spreading.
Future research could also lead to more specific ways to target neutrophils in the lung. The M18/2 antibody the researchers used in this study isn’t specific to neutrophils in the lung, which means it could come with unwanted side-effects.
While we may have found our way out of this traffic jam, we still have a long road ahead. That’s why we’re researching now. So that with your support, we can change the future of breast cancer.
This project was majority funded by us and supported by Cancer Research UK. You can find the original publication in Cell Reports.
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