Understanding the coordination of mechanical and biochemical factors in the spread of oral cancer
DOI: 10.1063/10.0042175
Understanding the coordination of mechanical and biochemical factors in the spread of oral cancer lead image
Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer. In OSCC tumors, epithelial cells may undergo epithelial-to-mesenchymal transition (EMT), transforming into mobile mesenchymal cells that can exit the tumor and invade nearby tissues.
Previous work has shown that in OSCC, EMT can be induced by either extracellular matrix stiffness and cytokine networks or small signaling proteins. Moon et al. sought to better understand how these two factors work together. They found that stiffness-induced mesenchymal cells, which were originally oral epithelial cells, were able to induce EMT in epithelial cells through cytokine secretion.
The results demonstrate how mechanical cues and biochemical cytokine signaling can work together to enhance OSCC tumor migration.
“This could be a unique mechanism used by cells, where they are first mechanically primed and then spread their bad behavior to adjacent cells that have not yet sensed the stiffness of the tumor and converted themselves,” said author Adam Engler. “While stiffness-induced EMT and cytokine-driven EMT have been studied independently, our work shows how mechanical cues propagate through cytokine networks to reshape surrounding epithelial behavior.”
The authors identified elevated levels of five cytokines in the mesenchymal cells, and their experiments showed that the cytokines enhanced motility and EMT. This work suggests that these cytokines, and the signaling pathways activated downstream of them, could be targeted in the treatment of OSCC.
“Moreover, the five-cytokine signature could inform risk stratification or saliva-based diagnostics for early detection of aggressive OSCC subtypes,” Engler said.
Next, the authors plan to validate their results in 3D OSCC models.
Source: “Stiffness-mediated paracrine signaling enhances Induction of EMT in Oral Squamous Cell Carcinoma,” by So Youn Moon, Marcelo Lazzaron Lamers, and Adam J. Engler, APL Bioengineering (2025). The article can be accessed at https://doi.org/10.1063/5.0299456 .
