Folds in tissue may unfold cancer

A recent study argues that the folds in wrinkled body tissue may tell much more than age—they may also promote and signal cancer.

Epithelia are layers of cells that make up the tissue that covers body parts such as skin and internal organs. Although previous studies demonstrated that the physical properties of cancerous epithelia facilitate the progression of the epithelial cancer, the details of this process have remained unclear. Such incomplete understanding leaves an untapped pool of additional approaches for diagnosing and treating epithelial cancers. Researchers at ETH Zürich and University Hospital Basel sought to address these limitations by exploring how the mechanical properties of epithelial tissue may induce and indicate cancer.

Using bladder cancer mouse models, microscopy, and computational continuum mechanics, the researchers reached two key conclusions. Compared to mice in the control condition, the researchers found that the bladder tissue of mice chemically induced to develop bladder cancer had an overgrowth of cells and aberrant buckling in the layers containing these cells. Importantly, the overgrowth and folds sometimes preceded the onset of physical characteristics that individual cancerous cells normally have. This is consistent with the possibility that cell overgrowth coupled with abnormal tissue folds can drive and predict cancer. Furthermore, in testing this possibility with computational simulations of overgrowing bladder tissue, the researchers observed that simulated changes to the stiffness of different bladder tissue layers could lead to cancer-like buckling in the tissue. These findings altogether suggest that the stiffness and, by extension, folds of epithelial tissue may support cancer.

Tissue stiffness and/or folds may thus be promising new markers in cancer diagnostics and treatment. Moreover, this study raises questions that may crucially inform new cancer detection and treatment methods, including how individual cells contribute to changes in tissue mechanics, to what extent the changed tissue mechanics cause or exacerbate cancer, and to what extent these mechanical changes are reversible.

Study credit: This study was led by Franziska Lampart and others at ETH Zürich, along with scientists at University Hospital Basel.

Managing correspondent: Wilaysha Evans

Research article: https://www.nature.com/articles/s41567-024-02735-2 (Nature Physics)

Press release article: https://www.nature.com/articles/s41567-024-02763-y (Nature Physics News and Views)

Image credit: Pixabay/envandrare