Cell migration is known to be triggered by constituents of the extracellular matrix such as fibronectin and by soluble mediators commonly summarized as motogens. Many growth factors such as the epidermal growth factor (EGF) have been shown to act as motogens. Recently, the secretory N-terminal portion of the beta-amyloid precursor protein (sAPP) has been identified as a keratinocyte growth factor. Hence, in this study we analysed whether sAPP stimulates also keratinocyte migration employing the stroboscopic cell motility assay. The migration velocity as well as the frequency of lamellipodia protrusion and ruffle formation were increased about two-fold thus corresponding to the effect of EGF. Using a newly developed beta1-integrin migration track assay we observed that sAPP increased the proportion of migrating keratinocytes and their directional persistence. sAPP appeared to operate synergistically with fibronectin with respect to its motogenic effect. Using a modified Boyden chamber assay we showed that sAPP besides its chemokinetic effect functions as a chemoattractant. Like EGF, sAPP exerted its motogenic effect through the activation of Rac kinase but the receptor for sAPP appears to be distinct. The results suggest that sAPP operates as a motogen in the human epidermis, where it may participate in the regulation of reepithelialization during wound healing.

中文翻译：

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分泌的β-淀粉样蛋白前体蛋白是人表皮角质形成细胞的运动原。

已知细胞迁移是由细胞外基质的成分（如纤连蛋白）和通常被概括为运动原的可溶性介体触发的。许多生长因子，例如表皮生长因子（EGF）已被证明可产生运动原。最近，β-淀粉样蛋白前体蛋白（sAPP）的分泌性N末端部分已被确定为角质形成细胞生长因子。因此，在这项研究中，我们使用频闪镜细胞运动分析法分析了sAPP是否也刺激角质形成细胞迁移。迁移速度以及片状脂膜突出和褶皱形成的频率增加了约两倍，因此对应于EGF的作用。使用新开发的beta1-整合素迁移轨迹测定法，我们观察到sAPP增加了迁移角质形成细胞的比例及其方向持久性。sAPP就其致动作用而言似乎与纤连蛋白协同作用。使用改良的博伊登室测定法，我们表明sAPP除了具有化学动力学作用外，还具有化学吸引作用。像EGF一样，sAPP通过激活Rac激酶发挥其致癌作用，但sAPP的受体似乎很明显。结果表明，sAPP在人的表皮中起运动原的作用，在伤口愈合过程中它可能参与重新上皮的调节。使用改良的博伊登室测定法，我们表明sAPP除了具有化学动力学作用外，还具有化学吸引作用。像EGF一样，sAPP通过激活Rac激酶发挥其致癌作用，但sAPP的受体似乎很明显。结果表明，sAPP在人的表皮中起运动原的作用，在伤口愈合过程中它可能参与重新上皮的调节。使用改良的博伊登室测定法，我们表明sAPP除了具有化学动力学作用外，还具有化学吸引作用。像EGF一样，sAPP通过激活Rac激酶发挥其致癌作用，但sAPP的受体似乎很明显。结果表明，sAPP在人表皮中作为运动原，在伤口愈合过程中可能参与重新上皮的调节。