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Last spring, Sara introduced some of the ways tumors avoid being killed by both our own bodies’ defenses and the various treatments we throw at them; if you’ve kept up since then, you’ve read a lot about cancer biology and a tumor’s ability to send out signals to other cells that keep them alive and happy. Most cancer treatments focus on blocking those signals or enabling other cells to fight back. Unfortunately, even when we get really exciting results in a lab setting, these treatments often fail when we start testing them in patients. This happens for a variety of reasons that can mostly be condensed to: cancer is really really complicated. And we can’t recreate that perfectly in a dish or in an animal (yet!). Fortunately, a new method for studying tumors based on their physical properties might bring us a step closer.
Physical properties? What does that mean exactly? You probably already know that there are both solid and liquid cancers. If there’s a lump somewhere, it’s classified as a solid tumor. If the cancer forms in bodily fluids, like leukemia (which happens in the blood), it’s classified as a liquid tumor. But solid tumors aren’t just lumps that are the same consistency throughout. They’re filled with cells that are connected by various molecules, such as collagen, that make up a kind of mesh around everything else. This creates a growing mass that behaves a little like silly putty. Sometimes a tumor can be very stiff and rubbery, sometimes it can be syrupy, and how much water you add to your mix can affect those things. Unlike silly putty, sometimes a tumor can be both stiff and syrupy, in different areas. As biologists, it’s a tumor characteristic we often ignore because it’s hard to measure and for a long time, it wasn’t thought to be important. But a group of physicists at the Institute of Light and Matter in France recently published a method for imaging tumors that uses a special microscope to create heat maps that provide information about how fluid is going in and out of the tumor, and where it’s stiff. Using this method (which, if you feel like going down a physics rabbit hole, is called Brillouin light scattering microscopy – BLS), they were able to identify predictors of invasiveness AND response to treatment, which are both vital and traditionally difficult to do outside of testing in humans.
The researchers used clumps of different types of cancer cells to show the potential of this method. First, they were able to compare two cancer types where one is known to be much more likely to spread throughout the body. Using their microscope, they shot lasers at these clumps (cool, right?) and found that one cancer type was better at “relaxing” than the other. Here, I use relax to describe how the cells behave under pressure, and I mean actual pressure! Picture a brand new sponge.
It’s fairly rigid and will stay intact each time you apply pressure, squeezing it to wring out the water. Then picture an old sponge. You should’ve replaced it by now – it’s softer and the outer edges are pretty raggedy. When you squeeze it, pieces of it flake off. Tumors are similar; fluid flows in and out of them, and, importantly, some of them might have little pieces escape as a response to pressure. Those are the ones to worry about as it means the cancer is more likely to spread. Normally, in order to study a tumor-sponge, you would break it up into individual pieces and study those. And you might find that the worn pieces on the outside look or behave differently than the pieces from the inside, but without techniques like the one this article is describing, you wouldn’t understand the whole picture as to why and what to do about it.
Even more promising, these researchers used this technique to better predict which chemotherapeutic drugs will work best on which tumor, and suggest other drugs that might be able to help current treatments work better. They used their BLS microscope on clumps of cancer cells undergoing treatment to learn things like how long it took the drug to reach the core of the clump. This is why fluid flow is so important. In the future, this technique can be used not only to inform decisions about which drugs to use, but also to learn more about how cancer cells react to those drugs and, as a result, how to decide on an effective dose. Whatever happens with BLS microscopy, one thing is becoming clearer in cancer research every day: studying tumors in 3 dimensions is a lot more important that we thought, and methods like these are essential to moving cancer research forward.
Margueritat, J., Virgone-Carlotta, A., Monnier, S., Delanoë-Ayari, H., Mertani, H. C., Berthelot, A., … & Dehoux, T. (2019). High-frequency mechanical properties of tumors measured by Brillouin light scattering. Physical Review Letters, 122(1), 018101.
Interstitial fluid: The overlooked component of the tumor microenvironment? – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/The-interstitial-space-in-normal-tissue-and-tumors-Top-The-interstitium-ie-loose_fig1_45284880 [accessed 14 Jan, 2019]
Header image created from Pixabay stock images in accordance with their license