Bulky glycocalyx shields cancer cells from invasion-associated stresses

The glycocalyx-that forms a protective barrier around cells-has been implicated in cancer cell proliferation, survival, and metastasis. However, its role in maintaining the integrity of DNA/nucleus during migration through dense matrices remains unexplored. In this study, we address this question by first documenting heterogeneity in glycocalyx expression in highly invasive MDA-MB-231 breast cancer cells, and establishing a negative correlation between cell size and glycocalyx levels. Next, we set-up transwell migration through 3 mu m pores, to isolate two distinct sub-populations and to show that the early migrating cell sub-population possesses a bulkier glycocalyx and undergoes less DNA damage and nuclear rupture, assessed using gamma H2AX foci formation and nuclear/cyto-plasmic distribution of Ku70/80. Interestingly, enzymatic removal of glycocalyx led to disintegration of the nuclear membrane indicated by increased cytoplasmic localisation of Ku70/80, increased nuclear blebbing and reduction in nuclear area. Together, these results illustrate an inverse association between bulkiness of the glycocalyx and nuclear stresses, and highlights the mechanical role of the glycocalyx in shielding migration associated stresses.

Automated summary

The glycocalyx, a protective barrier surrounding cells, has been found to play a role in cancer cell proliferation, survival, and metastasis. However, its function in maintaining DNA/nuclear integrity during migration through dense matrices has not been explored. This study shows that the bulkiness of the glycocalyx is inversely associated with nuclear stresses, and highlights its mechanical role in shielding migration-associated stresses.