Rapid Pressure Buildup Increases Cancer Cells' Propensity to Metastasize [Reading Science]

IBS Develops Sensor to Measure Pressure Inside Tumors Using MRI
Study Identifies How the Rate of Pressure Increase Affects Cancer Cell Motility and Invasiveness

It has been found that when pressure inside cancer tissue rises rapidly, cancer cells become more likely to spread to other tissues. Not only the magnitude of the pressure but also how quickly it rises affects cancer cells' propensity to metastasize. A Korean research team confirmed this phenomenon by developing a sensor that measures pressure inside living tumors using magnetic resonance imaging (MRI).

Schematic diagram showing changes in cancer cells' metastatic propensity depending on the rate of pressure increase. A gradual increase in pressure weakens their propensity to metastasize, while a rapid increase strengthens it. Provided by the research team.

The Institute for Basic Science (IBS) announced on October 12 that a joint research team led by Cheon Jinwoo, director of the IBS Center for Nanomedicine and an Underwood Professor at Yonsei University, and Jeon Youngwook, a professor at the University of California, San Francisco (UCSF), had developed an "M-Cube (M3)" sensor to measure pressure inside tumors with MRI and identified how pressure changes affect cancer cells' propensity to metastasize. The findings were published in the international journal Nature Nanotechnology on September 28.

As tumors grow, they push against surrounding tissue, and pressure builds up inside them. Although it was already known that this physical pressure affects cancer cell behavior, it had been difficult to directly measure how pressure changes deep inside living tumors. Existing optical sensors and microscopes have limitations when it comes to observing tissue deep inside the body, where light cannot readily reach, over extended periods.

Measuring "Invisible Pressure" Inside Tumors with MRI

The M-Cube sensor developed by the research team consists of an alginate hydrogel, a gel made from a substance derived from seaweed, containing tiny magnetic nanoparticles. When pressure is applied, the hydrogel contracts, changing the environment of water molecules around the magnetic nanoparticles inside it and altering the MRI signal.

Using this principle, the team successfully measured pressures ranging from 1 to 15 kilopascals (kPa) inside tumors. In particular, they were able to examine the distribution of pressure in spaces smaller than a millimeter, making it possible to identify which areas inside a tumor experience concentrated pressure.

The team analyzed how cancer cells respond to changes in pressure using tumor organoids, three-dimensional cell cultures that mimic the characteristics of actual tumors, and animal models.

Research findings tracking pressure changes inside living tumors using M-Cube sensors and MRI. Different pressure stresses were observed in regions with high and low metastatic potential, and the mechanisms by which pressure changes affect cancer cell motility and invasiveness were also identified. Courtesy of the research team.

The results showed no distinct changes in cancer cells when pressure increased slowly. In contrast, when pressure rose rapidly, oxidative stress increased substantially inside the cells, and the activity of genes associated with the YAP/TAZ proteins, which respond to physical stimuli, increased.

At the same time, connections between cancer cells loosened, and the process known as epithelial-mesenchymal transition (EMT), which gives cells the ability to move into or invade surrounding tissue, was also promoted. EMT is a key process involved in metastasis, in which cancer cells detach from their original tissue and spread to other parts of the body.

The Rate of Change Matters as Much as the Magnitude of Pressure

This study showed that not only the magnitude of the physical pressure acting on cancer cells but also the rate at which it rises may be an important factor in changing their behavior.

The study is significant because it linked physical stimuli to biological responses in cancer cells by using MRI to track changes in pressure inside tumors, which had previously been difficult to observe.

Researchers, from left: Cheon Jinwoo, director of the IBS Center for Nanomedicine and corresponding author; Jeon Youngwook, professor at UCSF and corresponding author; and Ahn Minji, postdoctoral researcher at the IBS Center for Nanomedicine and first author. Photo provided by IBS.

However, the study identified characteristics that favor metastasis, including increased cancer cell motility and invasiveness. It did not develop a technology to predict or diagnose the spread of cancer to other organs in actual patients. Further research is needed to determine whether the same phenomenon occurs in human cancer tissue.

The research team expects the M-Cube sensor to be useful not only in cancer research but also in identifying the effects of physical pressure in a range of biological processes, including tissue regeneration, inflammation, and fibrosis.

"This study used MRI to track the 'invisible forces' inside living tumors and revealed that changes in the pressure stress acting on cancer cells are closely linked to their propensity to metastasize," said Cheon Jinwoo, director of the IBS Center for Nanomedicine. "We expect the M-Cube sensor to help clarify the role of physical forces in a range of biological processes, including not only cancer metastasis but also tissue regeneration, inflammation, and fibrosis."

This content was produced with the assistance of AI translation services.