As our cells interact with neighboring cells or surrounding material known as the extracellular matrix, they are subjected to subtle mechanical stresses that can influence their behavior. Part of this includes heightened proliferation and tissue growth as the cells come under tension, and a new study on cancer cells has pinpointed the biological mechanism that drives this process, which the authors believe can be targeted to prevent tumor development.
Carried out by scientists at the University of Illinois Urbana-Champaign, the study centers on proteins called cadherins, which are likened to Velcro for the role they play in binding cells and tissues together. When doing so they adhere to growth factor receptors, which prevents communication between those receptors and growth factor proteins, robbing the tissue of the substance it needs to grow.
The scientists set out to see how intracellular tension can influence this relationship in human carcinoma cells, and alter the way they turn mechanical cues into biochemical signals. The experiments involved what's described as a "cell stretcher," in which the carcinoma cells were grown on a flexible medium to form a thin layer on top.
This enabled the scientists to stretch the cells out to place them under tension, which brought about changes in signaling that aligned with tissue growth and tumor development. The increased tension, the team found, counters the communication breakdown between the growth factor receptors and proteins, and triggers the activation of growth signaling pathways.
“This study confirms that cadherins use force to switch on biochemical growth signaling,” Leckband said. “By confirming these force-induced disruptions, we may be able to find a way to mutate cadherin molecules in order to prevent certain types of tissue growth, such as metastatic transformation and tumorigenesis.”
Manipulating the so-called "molecular Velcro" may therefore present a new way to tackle cancer, but such an approach is some way from clinical use. The scientists have so far only demonstrated these effects in human epithelial tissue, and will now build on these results by conducting similar experiments in in vitro human breast tissue.
The research was published in the journal Proceedings of the National Academy of Sciences.