Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.
Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Nat Rev Cancer. 2021 Sep;21(9):592-604. doi: 10.1038/s41568-021-00376-8. Epub 2021 Jul 8.
Collective cancer invasion with leader-follower organization is increasingly recognized as a predominant mechanism in the metastatic cascade. Leader cells support cancer invasion by creating invasion tracks, sensing environmental cues and coordinating with follower cells biochemically and biomechanically. With the latest developments in experimental and computational models and analysis techniques, the range of specific traits and features of leader cells reported in the literature is rapidly expanding. Yet, despite their importance, there is no consensus on how leader cells arise or their essential characteristics. In this Perspective, we propose a framework for defining the essential aspects of leader cells and provide a unifying perspective on the varying cellular and molecular programmes that are adopted by each leader cell subtype to accomplish their functions. This Perspective can lead to more effective strategies to interdict a major contributor to metastatic capability.
肿瘤细胞的集体侵袭和级联转移是目前癌症转移研究领域的热点问题。研究发现，肿瘤细胞在转移过程中形成的侵袭前沿具有明显的组织样结构，其中的“领导者”细胞能够在细胞外基质中“开辟道路”，并引导后续细胞的迁移，这种“领导者-跟随者”的组织样结构是肿瘤转移的主要机制之一。随着实验和计算模型及分析技术的最新进展，文献中报道的“领导者”细胞的特定特征和功能正在迅速扩展。然而，尽管它们很重要，但对于“领导者”细胞是如何产生的以及它们的基本特征，目前还没有共识。在本观点文章中，我们提出了一个定义“领导者”细胞基本特征的框架，并对不同的细胞和分子程序进行了统一的分析，这些程序被每个“领导者”细胞亚型采用来完成它们的功能。这一观点可能会为抑制转移能力的主要贡献者提供更有效的策略。
