Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared with normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate, utilizing several cell lines from the breast and lung. Initial screening was performed in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of the growth media used. Given the paradigm-shifting nature of our discovery, we pursued the mechanisms that could be responsible. Neither mass, cell doubling, nor volume accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of intracellular ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased intracellular ATP at premigratory-wound induction, but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.
细胞运动对于生存、繁殖、正常胚胎发育、再生以及伤口愈合至关重要。细胞迁移是转移的主要组成部分,而转移占所有实体瘤死亡病例的三分之二。尽管许多研究表明,与正常细胞相比,癌细胞的能量需求、代谢率和迁移能力均有所增加,但很少有研究系统性地并排比较正常细胞与癌细胞的迁移能力及其能量需求。因此,我们利用来自乳腺和肺的几种细胞系,研究了非恶性和恶性细胞的迁移方式。我们以无偏倚的高通量方式对细胞在胶原蛋白和/或基质胶上的迁移/侵袭能力进行了初步筛选。出乎意料的是,无论使用何种生长培养基,所有非恶性肺细胞的移动速度均显著快于源自肺肿瘤的细胞。鉴于这一发现具有颠覆性,我们进一步探究了可能的机制。细胞质量、倍增时间或体积均无法解释正常细胞的个体速度和轨迹长度。在迁移前伤口诱导阶段,非恶性细胞具有更高水平的细胞内ATP。与此同时,癌细胞在迁移前伤口诱导阶段也增加了细胞内ATP水平,但未达到正常细胞的水平,这为进一步的治疗研究提供了可能性。