Dutta Diganta, Palmer Xavier-Lewis, Ortega-Rodas Jose, Balraj Vasundhara, Dastider Indrani Ghosh, Chandra Surabhi
Department of Physics and Astronomy, University of Nebraska at Kearney, Kearney, NE, USA.
Department of Biomedical Engineering, Old Dominion University, Norfolk, VA, USA.
Breast Cancer (Auckl). 2020 Nov 12;14:1178223420972362. doi: 10.1177/1178223420972362. eCollection 2020.
Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, MDA-MB-231), and human normal mammary epithelial cells (MCF-10A), under different levels of glycemic stress. These were used to study both benign and malignant breast tissue behaviors. Benign cells (MCF-10A) recorded higher Young's modulus values than malignant cells (MCF-7 and MDA-231) under normoglycemic conditions, which agrees with the current literature. Moreover, exposure to high glucose (for 48 hours) decreased Young's modulus in both benign and malignant cells, to the effect that the cancer cells showed a complete loss in elasticity with high glucose. This provides a possible insight into a link between glycemic stress and cytoskeletal strength. This work suggests that reducing glycemic stress in cancer patients and those at risk can prove beneficial in restoring normal cytoskeletal structure.
糖尿病会加速癌细胞的增殖和转移，尤其是胰腺癌、肝癌、乳腺癌、结肠癌和皮肤癌。尽管已经广泛探索了连接这两种疾病状态的途径，但关于葡萄糖是否会引起细胞结构变化从而使癌细胞易呈现侵袭性表型，目前仍缺乏相关信息。因此，研究人员推测，与正常细胞相比，暴露于糖尿病/高糖环境中会使癌细胞的生物力学和生物物理特性发生更大改变，这有助于癌症进展。在本研究中，通过在不同程度的血糖应激下对多种人类乳腺癌细胞（MCF-7、MDA-MB-231）和人类正常乳腺上皮细胞（MCF-10A）进行微观探测，使用了原子力显微镜压痕技术。这些细胞被用于研究良性和恶性乳腺组织的行为。在正常血糖条件下，良性细胞（MCF-10A）的杨氏模量值高于恶性细胞（MCF-7和MDA-231），这与当前文献一致。此外，暴露于高糖环境（48小时）会降低良性和恶性细胞的杨氏模量，结果显示癌细胞在高糖环境下弹性完全丧失。这为血糖应激与细胞骨架强度之间的联系提供了一个可能的见解。这项研究表明，降低癌症患者及有风险人群的血糖应激可能有助于恢复正常的细胞骨架结构。
