Cell membranes are covered with sugar-conjugated proteins. New findings suggest that the physical properties of this coating, which is more pronounced in cancer cells, regulate cell survival during tumour spread.
The cell membrane serves as a signalling interface that allows cells to exchange information with their environment. It is constructed from lipids and contains both transmembrane and lipid-tethered proteins, which can be further modified through the covalent addition of sugars to build glycoproteins. Cancer cells frequently have higher levels of glycoproteins, such as mucin-1, than do healthy cells, and individual glycoproteins can transduce environmental signals that directly promote malignancy. However, glycoproteins also collectively organize into a glycocalyx.
Integrins are transmembrane receptors that bind extracellular matrix (ECM) proteins and are key interpreters and integrators of both the biochemical composition and the mechanical properties of the extracellular space. Cells with a thick glycocalyx are more efficient at receiving cell-survival signals through integrins, owing to the kinetic-trap properties of the glycocalyx. This may facilitate metastatic spread by enabling cancer cells to survive in the varied tissue and fluid environments they must traverse to colonize distant organs.
Integrin-based cell-matrix signalling is important for many steps in metastasis, including the migration of cancer cells out of the primary tumour and through the ECM, their entry into the vasculature, survival in the circulation, adhesion to the vessel wall, exit from the vasculature, and migration to and proliferative expansion in a distant organ. By reducing the rate of integrin binding and promoting clustering at existing adhesion sites, bulky glycoproteins act to promote a stable interaction between the cancer cells and the ECM.