Glycolytic oscillations in HeLa cervical cancer cell spheroids
Glycolytic oscillations in HeLa cervical cancer cell spheroids
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DOI：
10.1111/febs.16454
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发表时间：
2022-04-15
期刊：
影响因子：
5.4
通讯作者：
Yamaguchi, Tomohiko
中科院分区：
文献类型：
--
作者：
Amemiya, Takashi;Shibata, Kenichi;Yamaguchi, Tomohiko
先前的研究已经利用单层培养系统揭示了癌细胞（如HeLa宫颈癌和DU145前列腺癌细胞）中的糖酵解振荡。在这里，我们证明了HeLa宫颈癌细胞球体中的糖酵解振荡。实验表明，球体中有少量HeLa细胞表现出比单层更高频率的非均匀振荡。模型分析和我们之前的实验表明，球状体中振荡频率较高的主要原因是细胞中糖酵解酶活性的增加，葡萄糖从表面扩散到球体内部的运输降低了葡萄糖浓度，以及通过球体形成增加了细胞密度。这些结果和我们之前的研究表明，恶性肿瘤细胞比恶性肿瘤细胞更倾向于表现出更高频率的糖酵解振荡。球体中相邻的细胞在10%的频率差异内振荡，但彼此不同步。这表明在球形微环境中，与钙粘蛋白相关的HeLa细胞之间可能存在弱的细胞间相互作用；然而，相互作用不足以诱导糖酵解振荡的同步。
Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell-to-cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.