EXPRESSION OF COMPLETE KERATIN FILAMENTS IN MOUSE L-CELLS AUGMENTS CELL-MIGRATION AND INVASION
EXPRESSION OF COMPLETE KERATIN FILAMENTS IN MOUSE L-CELLS AUGMENTS CELL-MIGRATION AND INVASION
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DOI：
10.1073/pnas.90.9.4261
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发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
HENDRIX, MJC
中科院分区：
文献类型：
--
作者：
CHU, YW;RUNYAN, RB;HENDRIX, MJC
中间丝蛋白已被用来诊断特定细胞的起源。传统上，波形蛋白存在于间充质细胞中，角蛋白存在于上皮细胞中。然而，最近的证据表明，这些表型特异性蛋白的共表达增强了肿瘤细胞的运动性，从而增强了转移。在本研究中，我们使用小鼠 L 细胞模型来确定这些细胞中额外角蛋白的表达（通常仅表达波形蛋白）与其迁移能力之间是否存在直接相关性。用人角蛋白8、18以及8和18两者转染小鼠L细胞。结果表明，与亲本和对照转染克隆相比，表达完整角蛋白丝的细胞具有更高的迁移和侵袭能力（通过细胞外基质包被的过滤器）。此外，通过连续迁移选择的异质 L 克隆群体中存在角蛋白阳性细胞的富集。这种迁移活性与细胞在基质胶基质上的铺展能力直接相关，其中与其他L细胞群相比，角蛋白阳性转染子在更长的时间内保持圆形形态。总的来说，这些数据表明角蛋白可能通过与细胞外环境的特殊相互作用在迁移中发挥重要作用，从而影响细胞形状。
Intermediate filament proteins have been used to diagnose the origin of specific cells. Classically, vimentin is found in mesenchymal cells, and keratins are present in epithelial cells. However, recent evidence suggests that the coexpression of these phenotype-specific proteins augments tumor cell motility, and hence, metastasis. In the present study, we used the mouse L-cell model to determine if a direct correlation exists between the expression of additional keratins in these cells, which normally express only vimentin, and their migratory ability. Mouse L cells were transfected with human keratins 8, 18, and both 8 and 18. The results indicate that the cells expressing complete keratin filaments have a higher migratory and invasive ability (through extracellular matrix-coated filters) compared with, the parental and control-transfected clones. Furthermore, there is an enrichment of keratin-positive cells from a heterogeneous population of L clones selected over serial migrations. This migratory activity was directly correlated with the spreading ability of the cells on Matrigel matrix, in which the keratin-positive transfectants maintain a round morphology for a longer duration, compared with the other L-cell populations. Collectively, these data suggest that keratins may play an important role(s) in migration, through a special interaction with the extracellular environment, thereby influencing cell shape.