Department of Pathology, Moores Cancer Center, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Department of Pathology, Moores Cancer Center, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
Trends Cell Biol. 2024 May;34(5):380-387. doi: 10.1016/j.tcb.2023.08.001. Epub 2023 Aug 26.
While the tumor microenvironment is a critical contributor to cancer progression, early steps of tumor initiation and metastasis also rely on the ability of individual tumor cells to survive and thrive at locations where tumor stroma or immune infiltration has yet to be established. In this opinion article, we use the term 'isolation stress' to broadly describe the challenges that individual tumor cells must overcome during the initiation and expansion of the primary tumor beyond permissive boundaries and metastatic spread into distant sites, including a lack of cell-cell contact, adhesion to protumor extracellular matrix proteins, and access to nutrients, oxygen, and soluble factors that support growth. In particular, we highlight the ability of solitary tumor cells to autonomously generate a specialized fibronectin-enriched extracellular matrix to create their own pericellular niche that supports tumor initiation. Cancer cells that can creatively evade the effects of isolation stress not only become more broadly stress tolerant, they also tend to show enhanced stemness, drug resistance, tumor initiation, and metastasis.
虽然肿瘤微环境是癌症进展的关键因素，但肿瘤起始和转移的早期步骤也依赖于单个肿瘤细胞在肿瘤基质或免疫浸润尚未建立的位置生存和生长的能力。在这篇观点文章中，我们使用“隔离应激”一词来广泛描述单个肿瘤细胞在原发性肿瘤的起始和扩张超出允许边界以及转移到远处部位时必须克服的挑战，包括缺乏细胞-细胞接触、与促肿瘤细胞外基质蛋白的黏附，以及获取支持生长的营养物质、氧气和可溶性因子。特别是，我们强调了孤立肿瘤细胞自主生成富含纤维连接蛋白的细胞外基质的能力，以创建支持肿瘤起始的细胞周围生态位。能够创造性地逃避隔离应激影响的癌细胞不仅更能耐受广泛的应激，而且往往表现出增强的干性、耐药性、肿瘤起始和转移能力。
