Institut Pasteur, Department of Developmental and Stem Cell Biology, 25 rue du Dr. Roux, 75015 Paris, France.
Semin Cancer Biol. 2020 Jun;63:69-80. doi: 10.1016/j.semcancer.2019.05.004. Epub 2019 May 8.
The regulation of cell growth, cell proliferation and cell death is at the basis of the homeostasis of tissues. While they can be regulated by intrinsic and genetic factors, their response to external signals emanating from the local environment is also essential for tissue homeostasis. Tumour initiation and progression is based on the misregulation of growth, proliferation and death mostly through the accumulation of genetic mutations. Yet, there is an increasing body of evidences showing that tumour microenvironment also has a strong impact on cancer initiation and progression. This includes the mechanical constrains and the compressive forces generated by the resistance of the surrounding tissue/matrix to tumour expansion. Recently, mechanical stress has been proposed to promote competitive interactions between cells through a process called mechanical cell competition. Cell population with a high proliferative rate can compact and eliminate the neighbouring cells which are more sensitive to compaction. While this emerging concept has been recently validated in vivo, the relevance of this process during tumour progression has never been discussed extensively. In this review, I will first describe the phenomenology of mechanical cell competition focusing on the main parameters and the pathways regulating cell elimination. I will then discuss the relevance of mechanical cell competition in tumour initiation and expansion while emphasizing its potential opposing contributions to tumourogenesis.
细胞生长、增殖和死亡的调控是组织稳态的基础。虽然它们可以受到内在和遗传因素的调控，但它们对来自局部环境的外部信号的反应对于组织稳态也是至关重要的。肿瘤的发生和发展是基于生长、增殖和死亡的失调，主要是通过遗传突变的积累。然而，越来越多的证据表明，肿瘤微环境对癌症的发生和发展也有很强的影响。这包括机械约束和周围组织/基质对肿瘤扩张的阻力产生的压缩力。最近，机械应激被认为通过一种称为机械细胞竞争的过程促进细胞之间的竞争相互作用。具有高增殖率的细胞群体可以压缩并消除对压缩更敏感的邻近细胞。虽然这一新兴概念最近在体内得到了验证，但在肿瘤进展过程中，这一过程的相关性从未被广泛讨论过。在这篇综述中，我将首先描述机械细胞竞争的现象学，重点介绍调节细胞消除的主要参数和途径。然后，我将讨论机械细胞竞争在肿瘤起始和扩张中的相关性，同时强调其对肿瘤发生的潜在相反贡献。
