Jourquin Jérôme, Yang Neng, Kam Yoonseok, Guess Cherise, Quaranta Vito
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6840, USA.
J Cell Physiol. 2006 Feb;206(2):337-46. doi: 10.1002/jcp.20470.
We describe a model system in which cancer cell colonies disperse into single, highly migratory cells in response to lysophosphatidic acid (LPA). Though LPA is known to stimulate chemotaxis and chemokinesis, a colony dispersal effect has not been reported, to our knowledge. Cancer colony dispersal by LPA is comprised of an ordered sequence of events: (1) stimulation of membrane ruffling and formation of lamellipodia, (2) dissolution of adherens junctions, (3) single cell migration in a mesenchymal-like morphology we term "ginkgo-leaf." The net result is dispersal of carcinoma cells from a compact colony. We analyzed these three steps using live-cell imaging and computer-assisted quantification and measured the following parameters: onset of lamellipodia formation, lamellipodia velocity, colony dispersal, trans-epithelial resistance, migrating cell number and speed. Because hepatocyte growth factor (HGF) was described as an epithelial scatter factor, we compared it to LPA in our system and found that HGF has no epithelial colony dispersal properties and that this effect is strictly related to LPA. Given its striking similarity to tumor cell budding observed in patients, we propose that LPA-colony dispersal may provide a cellular mechanism underlying cancer invasion and as such deserves further studies.
我们描述了一种模型系统，在该系统中，癌细胞集落会响应溶血磷脂酸（LPA）而分散成单个具有高度迁移能力的细胞。据我们所知，尽管已知LPA能刺激趋化性和化学增活作用，但尚未有关于集落分散效应的报道。LPA诱导的癌细胞集落分散由一系列有序事件组成：（1）刺激膜皱襞形成和片状伪足形成；（2）黏附连接的溶解；（3）以我们称为“银杏叶”的间充质样形态进行单细胞迁移。最终结果是癌细胞从紧密的集落中分散开来。我们使用活细胞成像和计算机辅助定量分析了这三个步骤，并测量了以下参数：片状伪足形成的起始时间、片状伪足速度、集落分散情况、跨上皮电阻、迁移细胞数量和速度。由于肝细胞生长因子（HGF）被描述为一种上皮散射因子，我们在我们的系统中将其与LPA进行了比较，发现HGF没有上皮集落分散特性，且这种效应与LPA密切相关。鉴于其与在患者中观察到的肿瘤细胞出芽现象惊人相似，我们提出LPA - 集落分散可能为癌症侵袭提供一种细胞机制，因此值得进一步研究。
