Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Br J Cancer. 2021 Apr;124(9):1491-1502. doi: 10.1038/s41416-021-01309-w. Epub 2021 Mar 17.
Most cancer deaths are caused by metastasis: recurrence of disease by disseminated tumour cells at sites distant from the primary tumour. Large numbers of disseminated tumour cells are released from the primary tumour, even during the early stages of tumour growth. However, only a minority survive as potential seeds for future metastatic outgrowths. These cells must adapt to a relatively inhospitable microenvironment, evade immune surveillance and progress from the micro- to macro-metastatic stage to generate a secondary tumour. A pervasive driver of this transition is chronic inflammatory signalling emanating from tumour cells themselves. These signals can promote migration and engagement of stem and progenitor cell function, events that are also central to a wound healing response. In this review, we revisit the concept of cancer as a non-healing wound, first introduced by Virchow in the 19th century, with a new tumour cell-intrinsic perspective on inflammation and focus on metastasis. Cellular responses to inflammation in both wound healing and metastasis are tightly regulated by crosstalk with the surrounding microenvironment. Targeting or restoring canonical responses to inflammation could represent a novel strategy to prevent the lethal spread of cancer.
肿瘤细胞通过播散在远离原发肿瘤的部位而复发。大量的播散肿瘤细胞从原发肿瘤中释放出来，即使在肿瘤生长的早期阶段也是如此。然而，只有少数细胞能够存活下来，成为未来转移生长的潜在种子。这些细胞必须适应相对不利的微环境，逃避免疫监视，并从微转移阶段进展到宏观转移阶段，以产生继发性肿瘤。这种转变的一个普遍驱动因素是来自肿瘤细胞自身的慢性炎症信号。这些信号可以促进迁移和干细胞和祖细胞功能的参与，这些事件也是伤口愈合反应的核心。在这篇综述中，我们重新审视了癌症作为一种非愈合性伤口的概念，这一概念最早由 Virchow 在 19 世纪提出，并从肿瘤细胞内在的炎症角度关注转移。细胞对炎症的反应在伤口愈合和转移中都受到与周围微环境相互作用的严格调控。针对或恢复炎症的经典反应可能是预防癌症致命传播的一种新策略。
