Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036 TN, India.
Sci Rep. 2019 Jul 23;9(1):10684. doi: 10.1038/s41598-019-47116-5.
Physical cues are vital in determining cellular fate in cancer. In vitro 3D culture do not replicate forces present in vivo. These forces including tumor interstitial fluid pressure and matrix stiffness behave as switches in differentiation and metastasis, which are intricate features of cancer stem cells (CSCs). Gravity determines the effect of these physical factors on cell fate and functions as evident from microgravity experiments on space and ground simulations. Here, we described the role of simulation of microgravity (SMG) using rotary cell culture system (RCCS) in increasing stemness in human colorectal cancer cell HCT116. We observed distinct features of cancer stem cells including CD133/CD44 dual positive cells and migration in SMG which was not altered by autophagy induction or inhibition. 3D and SMG increased autophagy, but the flux was staggered under SMG. Increased unique giant cancer cells housing complete nuclear localization of YAP were observed in SMG. This study highlights the role of microgravity in regulating stemness in CSC and importance of physical factors in determining the same.
物理线索对于确定癌症中的细胞命运至关重要。体外 3D 培养无法复制体内存在的力。这些力包括肿瘤间质液压力和基质刚度，它们在分化和转移中起着开关的作用，而这些都是癌症干细胞（CSC）的复杂特征。重力决定了这些物理因素对细胞命运和功能的影响，这一点从太空和地面模拟的微重力实验中可以明显看出。在这里，我们描述了使用旋转细胞培养系统（RCCS）模拟微重力（SMG）对人结直肠癌细胞 HCT116 中干性增加的作用。我们观察到了癌症干细胞的明显特征，包括 CD133/CD44 双阳性细胞和迁移，而自噬的诱导或抑制并没有改变这些特征。3D 和 SMG 增加了自噬，但在 SMG 下通量是交错的。在 SMG 中观察到了具有完整核定位 YAP 的独特巨大癌细胞，这些癌细胞包含完整的核定位 YAP。这项研究强调了微重力在调节 CSC 干性中的作用，以及物理因素在决定干性方面的重要性。
