Nabeshima K, Moriyama T, Asada Y, Komada N, Inoue T, Kataoka H, Sumiyoshi A, Koono M
1st Department of Pathology, Miyazaki Medical College, Japan.
Clin Exp Metastasis. 1995 Nov;13(6):499-508. doi: 10.1007/BF00118189.
We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced invasion of Matrigel was associated with augmentation of cell motility but not with metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1. In a two-dimensional cell motility assay, TPA induced active L-10 cell locomotion with characteristic morphology; the cells moved outwards from the cell islands mainly as a localized coherent sheet of cells. The leading cells showed locomotor morphologies with fan-shaped leading lamellae while the following cells had cell contacts on all sides and appeared to lack leading lamellae. In the present ultrastructural study, the following cells frequently showed tapering cytoplasmic protrusions and leading lamella-like processes underlapping a preceding cell, indicating that the locomotion mechanism is almost the same for both the leading and following cells. For this type of locomotion as a coherent sheet we propose that localized modulation of cell-cell adhesion was induced such that wide intercellular gaps occurred at the lower portion of the cells to allow the cells to extend the tapering cytoplasmic processes and leading lamellae while close cell-cell contacts remained at the upper portion of the cells. These TPA-induced changes took place predominantly in the cells at the periphery of the cell islands, while the cells in the middle of the cell islands maintained close cell-cell contacts including complex interdigitation all around the cells, suggesting the modulation of TPA action by cell-cell interaction. Additionally, consistent with the evidence for junctional complexes between the cells moving outwards, the Lucifer-yellow dye transfer studies showed some, limited cell-cell coupling, suggesting the presence of at least some gap junctional intercellular communication in the moving cell sheets.
我们先前发现，在人直肠腺癌细胞系RCM-1的高转移变体（L-10）中，12-O-十四烷酰佛波醇-13-乙酸酯（TPA）增强的基质胶侵袭与细胞运动性增强相关，但与金属蛋白酶活性无关。在二维细胞运动分析中，TPA诱导活跃的L-10细胞运动，具有特征性形态；细胞主要以局部连贯的细胞片形式从细胞岛向外移动。领先的细胞呈现出具有扇形前缘片层的运动形态，而跟随的细胞在各面都有细胞接触，似乎没有前缘片层。在本超微结构研究中，跟随的细胞经常显示出逐渐变细的细胞质突起和覆盖在前一个细胞下方的前缘片层样突起，这表明领先细胞和跟随细胞的运动机制几乎相同。对于这种作为连贯片层的运动类型，我们提出诱导细胞间粘附的局部调节，使得在细胞下部出现宽的细胞间隙，以允许细胞延伸逐渐变细的细胞质突起和前缘片层，而在细胞上部保持紧密的细胞间接触。这些TPA诱导的变化主要发生在细胞岛周边的细胞中，而细胞岛中间的细胞保持紧密的细胞间接触，包括细胞周围的复杂交错，这表明细胞间相互作用对TPA作用有调节作用。此外，与向外移动的细胞之间存在连接复合体的证据一致，荧光黄染料转移研究显示了一些有限的细胞间偶联，表明在移动的细胞片中至少存在一些间隙连接的细胞间通讯。
