2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Exp Cell Res. 2013 Dec 10;319(20):3094-103. doi: 10.1016/j.yexcr.2013.08.018. Epub 2013 Aug 22.
The mortality of patients with solid tumors is mostly due to metastasis that relies on the interplay between migration and proliferation. The "go or grow" hypothesis postulates that migration and proliferation spatiotemporally excludes each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13 melanoma and 10 lung cancer) on both the individual cell and population levels. Following three-day-long videomicroscopy, migration, proliferation and cytokinesis-length were quantified. We found a significantly higher migration in mesothelioma cells compared to melanoma and lung cancer while tumor types did not differ in mean proliferation or duration of cytokinesis. Strikingly, we found in melanoma and lung cancer a significant positive correlation between mean proliferation and migration. Furthermore, non-dividing melanoma and lung cancer cells displayed slower migration. In contrast, in mesothelioma there were no such correlations. Interestingly, negative correlation was found between cytokinesis-length and migration in melanoma. FAK activation was higher in melanoma cells with high motility. We demonstrate that the cancer cells studied do not defer proliferation for migration. Of note, tumor cells from various organ systems may differently regulate migration and proliferation. Furthermore, our data is in line with the observation of pathologists that highly proliferative tumors are often highly invasive.
实体瘤患者的死亡率主要归因于转移，而转移依赖于迁移和增殖之间的相互作用。“走或长”假说假设迁移和增殖在时空上相互排斥。我们在个体细胞和群体水平上评估了 35 个细胞系（12 个间皮瘤、13 个黑色素瘤和 10 个肺癌）中的这一假说。经过为期三天的视频显微镜检查，我们量化了迁移、增殖和胞质分裂长度。我们发现间皮瘤细胞的迁移率明显高于黑色素瘤和肺癌细胞，而肿瘤类型在平均增殖或胞质分裂持续时间上没有差异。引人注目的是，我们发现黑色素瘤和肺癌细胞中的平均增殖与迁移之间存在显著的正相关。此外，非分裂的黑色素瘤和肺癌细胞表现出较慢的迁移。相比之下，间皮瘤细胞没有这样的相关性。有趣的是，黑色素瘤中细胞分裂长度与迁移之间存在负相关。高迁移率的黑色素瘤细胞中 FAK 的激活更高。我们证明，所研究的癌细胞不会为了迁移而延迟增殖。值得注意的是，来自不同器官系统的肿瘤细胞可能会以不同的方式调节迁移和增殖。此外，我们的数据与病理学家的观察结果一致，即高增殖性肿瘤通常具有高度侵袭性。
