Serrano Martinez Paola, Giuranno Lorena, Vooijs Marc, Coppes Robert P
Department of Biomedical Sciences of Cells and Systems-Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Cancers (Basel). 2021 Feb 18;13(4):855. doi: 10.3390/cancers13040855.
Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.
放射疗法参与多种癌症的治疗，但对周围正常组织造成的损伤往往不可避免。有证据表明，正常组织的稳态维持和再生是由特定的成体组织干/祖细胞驱动的。这些过程涉及多种信号通路的输入。辐射也会作用于这些干/祖细胞，引发旨在实现组织再生的细胞反应。在此，我们讨论目前用于研究辐射反应的体外和体内模型以及所涉及的特定组织干/祖细胞信号通路。结合使用具有高度体内相似性的复杂体外模型和解决器官复杂性的谱系追踪模型，构成了研究辐射后干/祖细胞反应的潜在工具。已发现Notch、Wnt、Hippo、Hedgehog和自噬信号通路对于驱动干/祖细胞辐射诱导的组织再生至关重要。我们综述了这些信号通路如何驱动实体组织特异性干/祖细胞对放射治疗的反应以及用于研究此问题的模型。
