School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Nat Rev Cancer. 2020 Mar;20(3):187-198. doi: 10.1038/s41568-019-0231-8. Epub 2020 Jan 13.
The tumour microenvironment plays a critical role in determining tumour fate. Within that environment, and indeed throughout epithelial tissues, cells experience competition with their neighbours, with those less fit being eliminated by fitter adjacent cells. Herein we discuss evidence suggesting that mutations in cancer cells may be selected for their ability to exploit cell competition to kill neighbouring host cells, thereby facilitating tumour expansion. In some instances, cell competition may help host tissues to defend against cancer, by removing neoplastic and aneuploid cells. Cancer risk factors, such as high-sugar or high-fat diet and inflammation, impact cell competition-based host defences, suggesting that their effect on tumour risk may in part be accounted for by their influence on cell competition. We propose that interventions aimed at modifying the strength and direction of cell competition could induce cancer cell killing and form the basis for novel anticancer therapies.
肿瘤微环境在决定肿瘤命运方面起着关键作用。在这个环境中,实际上在整个上皮组织中,细胞与邻近细胞竞争,那些适应性较差的细胞会被相邻的适应性较好的细胞淘汰。在这里,我们讨论了一些证据表明,癌细胞中的突变可能是因为它们能够利用细胞竞争来杀死邻近的宿主细胞而被选择出来的,从而促进肿瘤的扩张。在某些情况下,细胞竞争可以通过去除肿瘤和非整倍体细胞来帮助宿主组织抵抗癌症。癌症的危险因素,如高糖或高脂肪饮食和炎症,会影响基于细胞竞争的宿主防御,这表明它们对肿瘤风险的影响部分可能是由于它们对细胞竞争的影响。我们提出,旨在改变细胞竞争强度和方向的干预措施可能会诱导癌细胞死亡,并为新的抗癌疗法奠定基础。