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Cancer cells can rely on opportunism, as well as on chemical signaling, to spread through the body, according to new findings from mathematicians at the University of Birmingham.
The cancer spreads by sending cells from the primary tumor to cross the vascular or lymphatic system to colonize other organs as part of a process called metastasis. During this process, cancer cells must cross layers of endothelial cells – the cells that line the blood or lymphatic vessels.
Cancer cells were thought to transmit a chemical signal to endothelial cells, thus opening them to openings through which cancer could migrate, but a team of Birmingham researchers suggested that an alternative or complementary process might also be needed. l & # 39; work.
In collaboration with partners from the Mbadachusetts Institute of Technology, the University of Zaragoza and others, the team has developed a detailed mathematical model of endothelial cell behavior to show how and where openings appear in the endothelial layer and how long they stay open. .
Their results, published in PLOS Computational Biology, showed how the physical forces within the cell structure continuously push and pull cells in different directions, sometimes causing breaks in the links between them, leaving temporary spaces.
The researchers then tested this model on cell cultures of endothelial monolayers with cancer cells and observed how cancer cells could exploit this endothelial motion and migrate through the holes.
"The gaps in the endothelium open and close spontaneously, whether there are cancer cells or not," says lead researcher Dr. Fabian Spill, a senior lecturer in applied mathematics at the endothelium. the University of Birmingham.
"They are due to an interaction between mechanics and chemistry exerting different forces on cells.Many work has already been done to characterize the chemistry of the endothelium.Our work completes this research by putting the emphasis about the mechanical forces at work in these processes. "
Interestingly, the researchers also found that apertures were most likely to appear at junctions of three or more cells as opposed to two-cell boundaries. Cancer cells that had landed at the borders between two cells were able to migrate to these tricellular junctions where they fled. This indicates that cancer cells are able not only to signal to the endothelium to chemically open new openings, but that they can also employ an opportunistic wait-and-see approach. This allows them to take advantage of spontaneous formation of gaps in the endothelium.
In this study, the team focused on the vascular system. Future work will examine the lymphatic system or different types of endothelial cells, and will also focus on other factors contributing to the dynamics of endothelial gaps, such as blood flow and three-dimensional structure of the blood vessels, which will all affect the capacity of the cell. cancer cells to transmigrate.
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Notes to editors:
* Spill et al (2019). "The balance of mechanical forces causes formation of gaps in the endothelium and can facilitate cancer and extravasation of immune cells". PLOS Computational Biology. https: /
* The University of Birmingham is ranked among the top 100 institutions in the world. His work attracts people from around the world to Birmingham, including researchers and teachers, and more than 6,500 international students from more than 150 countries.
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