Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA; Tumor Microenvironment & Metastasis Program, Albert Einstein Cancer Center, Bronx, NY, USA.
School of Health & Life Sciences, Teesside University, Middlesbrough TS1 3BX, United Kingdom; National Horizons Centre, Teesside University, Darlington DL1 1HG, United Kingdom.
Cytokine Growth Factor Rev. 2024 Feb;75:12-30. doi: 10.1016/j.cytogfr.2023.10.003. Epub 2023 Oct 31.
The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF1), has emerged as a pivotal regulator in the intricate molecular networks driving cancer progression. As an influential factor in the tumor microenvironment, CXCL12 plays a multifaceted role that spans beyond its traditional role as a chemokine inducing invasion and metastasis. Indeed, CXCL12 has been assigned functions related to epithelial-to-mesenchymal transition, cancer cell stemness, angiogenesis, and immunosuppression, all of which are currently viewed as specialized biological programs contributing to the "metastatic cascade" among other cancer hallmarks. Its interaction with its cognate receptor, CXCR4, initiates a cascade of events that not only shapes the metastatic potential of tumor cells but also defines the niches within the secondary organs that support metastatic colonization. Given the profound implications of CXCL12 in the metastatic cascade, understanding its mechanistic underpinnings is of paramount importance for the targeted elimination of rate-limiting steps in the metastatic process. This review aims to provide a comprehensive overview of the current knowledge surrounding the role of CXCL12 in cancer metastasis, especially its molecular interactions rationalizing its potential as a therapeutic target.
趋化因子 CXCL12，也被称为基质细胞衍生因子 1（SDF1），已成为推动癌症进展的复杂分子网络中的关键调节因子。作为肿瘤微环境中的一个重要因素，CXCL12 发挥着多方面的作用，不仅仅局限于传统的趋化因子诱导侵袭和转移的作用。事实上，CXCL12 被赋予了与上皮间质转化、癌细胞干性、血管生成和免疫抑制相关的功能，所有这些功能目前都被认为是专门的生物学程序，有助于“转移级联”和其他癌症特征。它与其同源受体 CXCR4 的相互作用引发了一系列事件，不仅塑造了肿瘤细胞的转移潜力，还定义了支持转移定植的次级器官内的小生境。鉴于 CXCL12 在转移级联中的深远影响，了解其机制基础对于靶向消除转移过程中的限速步骤至关重要。本综述旨在全面概述 CXCL12 在癌症转移中的作用的现有知识，特别是其分子相互作用，为其作为治疗靶点的潜力提供理论依据。
