In breast cancers, dense tissue surrounding a tumour is often an indication of poor prognosis.
That density is caused by a tight network of cells and molecules like collagen in the tumour’s extracellular matrix (ECM), part of the tumour microenvironment.
You might have heard us talk about the ECM before. It’s acts like a scaffold that provides a tumour with the structural support it needs to grow.
But there’s a catch to having this dense support system. It makes it difficult for tumours to grow blood vessels, which limits their blood supply.
That poses a problem. Our blood flow is how we deliver vital nutrients like oxygen and sugars to our tissues. A limited blood supply means a limited supply of nutrients. Without nutrients, the tumours will starve.
So, to survive, cancer cells need to be able to adapt to find a new food source, and fast.
Previously, research has shown that when pancreatic cancer cells lack certain amino acids, the building blocks we need to make proteins, they can absorb proteins from their surrounding environment.
Then, they break them back down into amino acids, which they can use to make energy by utilising special chemical pathways.
That piqued the interest of a group of researchers at the University of Sheffield. They thought, if pancreatic tumour cells can absorb surrounding proteins to use as a source of amino acids, maybe breast cancer cells are using the dense ECM as a source of protein in a pinch.
“Cancer cells get so few nutrients from the blood, you’d think they can’t grow,” says Dr Elena Rainero, who led the Cancer Research UK-funded team.
“But since they are still growing, there must be other ways in which they can obtain enough food.”
“Our idea was that maybe the cells can use their matrix, this scaffold around them, as a source of nutrients because it’s composed of proteins, and proteins can be broken down.”
As the ECM provides the tumour with support, breaking it down to use for food might sound counterintuitive. But desperate times call for desperate measures.
A modified metabolism
To put this idea to the test, they grew groups of breast cancer cells in the lab, along with the molecules that you’d usually find in the ECM.
They then provided these groups of cells with different levels of nutrients. Some were given an unlimited supply of glucose, the sugar our cells use to make energy, and amino acids, whilst others had restricted amounts, mimicking the environment they’d grow in in the body.
And they found that the cells were doing what cancer cells do best: adapting.
Even in low nutrient conditions, the cells were able to grow, albeit not as quickly as the cells with full access to nutrients.
“Once we found that, we wanted to understand how the cells do it,” says Rainero.
“Is it because they are touching the matrix and that activates something inside the cells? Or is it because the cells are feeding on the matrix?
“When we looked into that, we found that the cells are actually able to take parts of the matrix in and digest them.”
That answered one question but raised another. If the cells were using something other than glucose to make energy, they must have modified their metabolism somehow.
So, what did they change?