糖萼-在细胞周围形成保护屏障-与癌细胞增殖有关,生存,和转移。然而,它在通过致密基质迁移过程中维持DNA/细胞核完整性的作用仍未被探索。在这项研究中,我们通过首先记录高度侵袭性MDA-MB-231乳腺癌细胞中糖萼表达的异质性来解决这个问题,并在细胞大小和糖萼水平之间建立负相关。接下来,我们建立了通过3微米孔的transwell迁移,为了分离两个不同的亚群,并表明早期迁移的细胞亚群具有较大的糖萼,并且经历较少的DNA损伤和核破裂,使用γH2AX灶形成和Ku70/80的核/细胞质分布进行评估。有趣的是,糖萼的酶促去除导致核膜的崩解,这表明Ku70/80的细胞质定位增加,核起泡增加和核面积减少。一起,这些结果说明了糖萼的体积与核胁迫之间的负相关,并强调了糖萼在屏蔽迁移相关应力中的机械作用。
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 µm 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 γH2AX foci formation and nuclear/cytoplasmic 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.