Department of Otolaryngology‑Head and Neck Surgery, College of Medicine, Korea University, Seoul 136‑705, Republic of Korea.
School of Biomedical Engineering, Korea University, Seoul 136‑705, Republic of Korea.
Int J Oncol. 2020 Jun;56(6):1490-1498. doi: 10.3892/ijo.2020.5016. Epub 2020 Mar 19.
Multicellular tumor spheroids (MTSs) of malignant cells can display cell‑cell and cell‑matrix interactions, different from monolayer cultures. The objective of the present study was to examine difference in intercellular and cell‑matrix interaction between monolayered cultures and spheroid cultures. Expression levels of cell adhesion molecules (CAMs) and epithelial‑mesenchymal transition (EMT) signaling molecules in monolayered cells and MTS cells were compared. The motility of single cells dispersed from each culture was evaluated using a live‑cell imaging device. The effect of an E‑cadherin neutralizing antibody, DECMA, was also compared between the two cultures. Among various CAMs, only E‑cadherin was increased in MTSs. The motility of single cells dispersed from MTSs was higher than that from monolayered cells. Compared with monolayered cells, the molecular weight (MW) of β1 integrin was decreased during MTS formation, particularly during the early stage. This notable reduction was maintained when DECMA was used to treat MTSs. Additionally, the expression levels of the EMT signaling molecules Snail and ILK increased more in MTSs than in monolayered cells. The blocking of E‑cadherin elicited increased expression levels of EMT molecules and cellular motility only in MTSs. In conclusion, the alteration of E‑cadherin expression and presence of low‑MW β1 integrin in MTS may enhance cell motility via the upregulation of EMT signaling molecules that may be intensified by blocking E‑cadherin.
多细胞肿瘤球体（MTSs）中的恶性细胞可以表现出细胞-细胞和细胞-基质相互作用，与单层培养不同。本研究的目的是研究单层培养和球体培养之间细胞间和细胞-基质相互作用的差异。比较了单层细胞和 MTS 细胞中细胞黏附分子（CAMs）和上皮-间充质转化（EMT）信号分子的表达水平。使用活细胞成像设备评估了从每种培养物中分散的单个细胞的迁移能力。还比较了两种培养物中 E-钙黏蛋白中和抗体 DECMA 的作用。在各种 CAM 中，只有 E-钙黏蛋白在 MTS 中增加。从 MTS 中分散的单个细胞的迁移能力高于从单层细胞中分散的单个细胞。与单层细胞相比，β1 整合素的分子量（MW）在 MTS 形成过程中降低，特别是在早期阶段。当使用 DECMA 处理 MTS 时，这种明显的减少得以维持。此外，与单层细胞相比，MTS 中 EMT 信号分子 Snail 和 ILK 的表达水平增加更多。仅在 MTS 中阻断 E-钙黏蛋白会引发 EMT 分子的表达水平增加和细胞迁移增加。总之，E-钙黏蛋白表达的改变和 MTS 中低 MW β1 整合素的存在可能通过上调 EMT 信号分子来增强细胞迁移，而阻断 E-钙黏蛋白可能会加剧这种作用。
