Cancer Cells Thrive in Body’s Sweet Spots: Study (newsweek.com)
An international team of researchers led by University of Minnesota Twin Cities engineers have found that cancer cells can gravitate toward certain mechanical “sweet spot” environments, providing new insights into how cancer invades the body. The findings could help scientists and engineers better understand how cancer spreads and could improve future treatments.
Cancer Cells Migrate Towards “Sweet Spot” Environments.
Published: July 13, 2022
| Original story from University of Minnesota Twin Cities
The study is published in Nature Materials, a peer-reviewed, multidisciplinary scientific journal.
In a previous study, the University of Minnesota-led team found that cells have the ability to sense the stiffness of their environment—which ranges from stiff (bone tissue) to soft (fatty tissue) to medium stiffness (muscle tissue)—and their ability to move is dependent upon that environment. Their research showed that the cells can have a “sweet spot” of stiffness, that isn’t too hard or too soft, in which they have better traction and can move faster.
In this study, the researchers found that not only does the stiffness of the environment impact the speed at which cells move, but it also affects the direction in which they move. For many years, scientists have thought that cells would always gravitate toward a stiffer environment, but the University of Minnesota researchers observed for the first time that cells can actually move toward a “sweet spot” that’s more in the middle.
“This discovery challenges the current thinking in the field, which is that cells only move toward stiffer environments,” said David Odde, a professor in the University of Minnesota Twin Cities Department of Biomedical Engineering and senior author of the study. “I think that this finding will change how people think about this phenomenon. Our mathematical model predicted, and we’ve shown through experiments, that cells actually can move toward the softer side.”
Cancer cells migrating toward a “sweet spot” – YouTube
The video above shows the migration of cancer cells over a span of 24 hours toward a
“Sweet spot” in the middle of stiff and soft environments, represented by the gray box at the bottom. Video credit: David Odde Laboratory, University of Minnesota.
During the study, Odde and his team looked at both brain cancer and breast cancer cells. They placed cells between two environments—a stiffer region and a softer region—and observed where they accumulated. The research team also found that some cells, like the breast cancer cells they studied, have a feedback mechanism that causes them to grip more strongly onto stiffer environments, which explains why many previous studies showed cells moving to the stiffer side.
However, if you turn that mechanism off genetically, the cells will then gravitate more toward the middle. “We’re basically decoding how cancer cells invade tissue,” Odde said. “They don’t just move randomly. They actually have particular ways in which they like to move, and if we can understand that we may be better able to trip them up.”
The next step for the researchers is to use this information to build a simulator that shows how cancer cells move through an entire tumor, which will help them better predict cells’ movements based on their environments.
Reference: Isomursu A, Park KY, Hou J, et al. Directed cell migration towards
softer environments. Nat Mater. 2022:1-10. doi: 10.1038/s41563-022-01294-2
This article has been republished from the following materials.
Note: material may have been edited for length and content.
For further information, please contact the cited source.
Study Reveals How Cancer Cells Thrive in Oxygen-Starved Tumors (osu.edu)
HEALTH & MEDICINE
Researchers take a closer look at cancer cells’ ability to rewire, thrive, and survive.
BY MGH News and Public Affairs
“We need to rethink how we are studying cancer metabolism’
Insights into how cancer cells adapt and rewire their metabolism to achieve growth and survive were accompanied by a call for tools to study this on a nearly single-cell level, according to a new paper in Nature Communications.
Fundamental cancer metabolism dogma revisited
by Massachusetts General Hospital
Glucose metabolism in cancer cells.
A new paper in Nature Communications reveals new insights into adaptations made
by cancer cells to rewire their metabolism to achieve growth and survive.
Among the discoveries are a challenge to a well-known feature in cancer metabolism, raising the call for tools to study cancer cell metabolism on a nearly single-cell level.
In the 1920s, Otto Warburg observed cancer cells metabolically adapt their glucose pathway in unusual ways. Normally, glucose—the main nutrient needed for cells to function—is sent to the cell’s mitochondria to be broken down for energy, a process
that requires oxygen.
However, cancer cells appear to rapidly increase their glucose uptake and directly
ferment it into lactate, even in the presence of oxygen and functional mitochondria.
“He called it aerobic glycolysis, but we know it as the Warburg effect,” says author
Raul Mostoslavsky, MD, Ph.D., scientific co-director of Mass General Cancer Center
and the Laurel Schwartz Professor of Oncology (Medicine) at Harvard Medical School.
For nearly 15 years researchers have been trying to explain why cancer cells do this.
In this paper, Mostoslavsky’s team studied colon cancer tumors to learn more.
They developed a fluorescent reporter that stained only a marker of glycolysis in cells of the tumor. Using this reporter and a mass spectrometry imaging approach developed by collaborator Nathalie Agar of Brigham and Women’s Hospital, the researchers found that not all cells within the colon cancer cell relied on Warburg glycolysis.
“We found that this metabolic adaptation does not happen in the whole tumor, only in a heterogeneous group that were not dividing,” says Mostoslavsky. His team had published this heterogeneous feature in squamous cell carcinoma, but this is the first time it has been shown in colon cancer, and in non-dividing cells. “What really surprised us is that when we stained the tumor cells with a marker of cell proliferation, they were mutually exclusive,” adds Mostoslavsky. Within fully transformed colon cancers, the cells that were doing Warburg glycolysis were not dividing.
“This completely challenges the dogma of the Warburg effect,” he adds. For the past 10 to 15 years, most researchers working in cancer metabolism have held that cancer cells do Warburg glycolysis to send glucose for biomass production, or rapid proliferation. “Instead, we found that the main reason they were doing it was to reduce reactive oxygen species, or ROS.” Reactive oxygen species damage cells during glucose breakdown and energy production: “The cells do Warburg metabolism to protect against accumulation of ROS.” This research showed that indeed Warburg glycolysis is real and functional in cancer cells as a needed adaptation.
Mostoslavsky Lab (massgeneral.org)
“But it’s not for the reason we used to think,” says Mostoslavsky.
“This means we need to rethink how we are studying cancer metabolism.”
Much of the advancements made in the past 10 years studying cancer metabolism come from mass spectrometry analysis of metabolomics, which require many cells.
The problem is a lack of means for analyzing cellular heterogeneity.
“If metabolic adaptation happens in some cancer cells or not in others, you will not be able to determine that with the current technologies that exist,” he says.
“We now know Warburg glycolysis is a heterogeneous feature happening in tumors so we need to develop tools that will allow us to investigate tumors in a single-cell fashion.”
In this paper, the team relied on a novel mass spectrometry imaging tool developed to achieve data almost at a single cell resolution. Says Mostoslavsky: “It is clear that cancer metabolism is highly heterogeneous so we will need new tools like this to study and define these metabolic features in tumors.”
Other authors of the study Carlos Sebastian, Christina Ferrer, Maria Serra, Jee-Eun Choi, Nadia Ducano, Alessia Mira, Manasvi Shah, Sylwia Stopka, Andrew Perciaccante, Claudio Isella, Daniel Moya-Rull, Marianela Vara-Messler, Silvia Giordano, Elena Maldi, Niyata Desai, Diane Capen, Enzo Medico, Murat Cetinbas, Ruslan Sadreyev, Dennis Brown, Miguel Rivera, Anna Sapino, and David Breault.
This work was supported by grants from the National Institutes of Health, FPRC 5 per mille 2011 MIUR, FPRC 5 per mille 2014 MIUR, RC 2018 Ministero della Salute, and the European Union’s Horizon 2020 Research and Innovation Program. This was adapted from a Massachusetts General Hospital press release.
Explore further
Greedy for glucose: Cancer cells rely on a primeval energy-producing pathway to proliferate and spread
More information: Carlos Sebastian et al, A non-dividing cell population with
high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine, Nature Communications (2022). DOI: 10.1038/s41467-022-29085-yJournal information: Nature Communications
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