A tumor around tumors can prevent the spread of cancer cells

For cancer cells to metastasize, they must first break free of the tumor’s own defenses. Most tumors are peeled in a “floor” protective ball – a thin, pliable film that keeps cancer cells in place as they grow and separate. Before spreading to other parts of the body, the cells have to break down the ground floor membrane, a substance that scientists themselves have found difficult to make.

MIT engineers have now examined the organs of breast cancer tumors and have found that the delicate coating is as hard as a plastic cover, but which is surprisingly elastic like a balloon. party, able to fit twice the original size.

But while a balloon becomes much easier to blow up after a little effort, the team found that an organ is harder as it expands.

This stiff but elastic quality may help organs control how tumors grow. The fact that the organs appear to stiffen as they expand suggests that they may inhibit tumor growth and their ability to diffuse, or metastasize, to at least partially. .

The findings, published this week in the Proceedings of the National Academy of Sciences, it could open a new path towards prevention Pile the ground floor which is the most common cause of cancer-related deaths.

“Now we can think of ways to add new substances or drugs to strengthen this strong effect, and increase the hardness of the organs to prevent cancer cells from breaking through, “said Ming Guo, lead author of the study and associate professor of mechanical engineering at MIT.

Guo’s co-authors include first author Hui Li of Beijing Normal University, Yue Zheng and Shengqiang Cai of the University of California at Santa Diego, and MIT postdoc Yu Long Han.

Blowing up

The basement membrane surrounds not only cancerous growth but also healthy tissues and organs. The film – a thick layer of human hair – serves as a physical support that holds joints and organs in place and helps shape their geometry, while keeping them unique and special.

Guo’s group specializes in the study of cell mechanics, with a focus on the behavior of cancer cells and the processes that drive tumors to metastasize. The researchers had been studying how these cells interact with their surroundings as they migrate through the body.

An urgent question we realized was that we didn’t get enough attention, what about the membrane around tumors ?. To find out, cells need to break down this layer. What is this level in terms of material properties? Is it something that cells need to work hard to break down? That’s what made us look into the ground floor organs. “

Ming Guo, Principal study author and Associate Professor, Mechanical Engineering, Massachusetts Institute of Technology

To measure organ features, scientists have employed an atomic force microscope (AFM), using a tiny mechanical probe to gently push the surface of the organ. The force required to deform the surface may give researchers an idea of ​​the strength or elasticity of a material.

However, as the basement ball is very thin and difficult to separate from underground weaving, Guo says it is difficult to deduce from AFM measurements what the membrane tension is, as well as the material underneath.

Instead, the team used a simple method, similar to blowing a balloon, to remove the ball and measure its elasticity. They first grew human breast cancer cells, which naturally break down proteins to form a ball around groups of cells called tumor spheroids.

They grew several spheroids of different sizes and inserted a glass microneedle into each tumor. They infiltrated the tumors with fluid at a controlled pressure, causing the organs to separate from the cells and go up like a balloon.

The researchers applied various steady weights to enlarge the organs until they reached a stable state, or to expand no further, and then removed the weight.

“It’s a very simple test that can tell you a few things,” Guo says. “One is, when you apply pressure to swallow this balloon, it grows a lot bigger than its original size. And as soon as you put out weight, it gradually shrinks. which is a classic carrier of elastic material, resembling rubber. balloons. “

Elastic knot

As they ascended each spheroid, the researchers noted that while the ability of an organ to penetrate and damage showed that it was generally muddy like a balloon, the miniatures more detailed information about this behavior is quite different.

Blowing up a latex balloon usually requires a lot of effort and pressure to get started. As soon as it gets going and starts to go a bit, the balloon will suddenly become much easier to explode.

“Usually, once the balloon’s radius rises to about 38 percent, you don’t have to blow harder – just maintain pressure and the balloon expands dramatically,” Guo explains. say.

This phenomenon, known as snap-through instability, is seen in balloons made of materials that are linear elastic, meaning that the sexual elasticity, or stiffness, does not change as they deform or go up.

But based on their measurements, the researchers found that the lower membrane instead of becoming harder, or more stable as it went up, showed that the invisible material is elastic, and able to change its stiffness as it deforms.

“If snap-through instability happened, a tumor would become an accident – it would just explode,” Guo says. “In this case, no. That shows me that the lower extremity is in control of growth.”

The team plans to measure organ features at different stages of cancer development, as well as transport it around healthy tissues and organs. They are also exploring ways to change the elasticity of the organs to see if it can harder prevent cancer cells from breaking through.

“We are actively pursuing how you can change the mechanics of these organs, and the effects they can have on breast cancer models, to see if we can delay the onset or metastasis,” Guo “This is like making a harder balloon, which we plan to try. “