Image: Visualization of the movement of the structures that cells use to exert force on their environment.
As every woman knows, an early test for breast cancer is feeling for lumps. What the doctor or patient herself is actually looking for when she does this is one of the first signs of tumor development: an unusual stiffening of the tissue. In fact, tissue stiffness is so crucial to tumor development that malignant (cancer-like) behavior can be caused in perfectly healthy breast cells simply by placing them in a stiffer environment. Until now, though, how cells could detect tissue stiffness and why they react differently in healthy versus malignant conditions had not been understood.
In a study published yesterday in Nature Materials
, researchers at the Institute for Bioengineering of Catalonia (IBEC), together with their colleagues at Queen Mary University of London’s Barts Cancer Institute, demonstrate how the molecules that cells use to attach to their environment, called integrins, allow the cells to detect and adapt to tissue rigidity.
The role of integrins
“In healthy breast cells, we have shown that the adhesive properties of integrins lead cells to reduce the force they apply to their environment if the tissue is stiffer than normal,” says Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, who led the study. “Because reducing force also reduces tissue stiffness, this mechanism can prevent tissue stiffening.”
However, cancer cells in the breast express a different type of integrin with different adhesive properties. This other integrin leads cells to apply higher forces as tissue stiffness increases, creating a feedback mechanism that can eventually lead to the hard lumps characteristic of breast tumors.
Preventing tissue stiffening, a possible tool against cancer
“Our study is the first time ever that a molecular mechanism of rigidity sensing by cells has been described, and it’s been demonstrated in healthy and unhealthy human breast cells,” says Pere. “Fascinatingly, abnormally rigid tissues are found not only in breast tumors but in several other types of cancer, which also express many different types of integrins. This means that mechanical changes induced by altered integrin expression could be a key aspect behind the onset of several diseases.”
The researchers now intend to investigate whether integrin regulation is indeed a general mechanism of mechanical control of tissues, both healthy and diseased. If so, this would have an enormous potential for possible therapies designed to prevent malignant alterations in tissue stiffness.
This work was supported in part by the Obra Social “la Caixa” within the framework of their pilot scheme for funding research evaluation and technology transfer.
Elosegui-Artola, A., Bazellières, E., Allen, M.D., Andreu, I., Oria, R., Sunyer, R., Gomm, J.J., Marshall, J.F., Jones, J.L., Trepat, X., Roca-Cusachs, P. (2014). Rigidity sensing and adaptation through regulation of integrin types. Nature Materials
, 13, 631–637