OncoRay - National Center for Radiation Research in Oncology, Medizinische Fakultät Carl Gustav Carus der Technischen Universität and Helmholtz Zentrum Rossendorf , Dresden.
Int J Radiat Biol. 2014 Aug;90(8):687-99. doi: 10.3109/09553002.2014.906766.
Radioresistance of cancer cells remains a fundamental barrier for maximum efficient radiotherapy. Tumor heterogeneity and the existence of distinct cell subpopulations exhibiting different genotypes and biological behaviors raise difficulties to eradicate all tumorigenic cells. Recent evidence indicates that a distinct population of tumor cells, called cancer stem cells (CSC), is involved in tumor initiation and recurrence and is a putative cause of tumor radioresistance. There is an urgent need to identify the intrinsic molecular mechanisms regulating the generation and maintenance of resistance to radiotherapy, especially within the CSC subset. The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. The interaction of CXCR4 with its ligand, the chemokine C-X-C motif ligand 12 (CXCL12), plays an important role in modulating the tumor microenvironment, angiogenesis and CSC niche. Moreover, the therapeutic inhibition of the CXCR4/CXCL12 signaling pathway is sensitizing the malignant cells to conventional anti-cancer therapy.
Within this review we are summarizing the role of the CXCR4/CXCL12 axis in the modulation of CSC properties, the regulation of the tumor microenvironment in response to irradiation, therapy resistance and tumor relapse.
In light of recent findings, the inhibition of the CXCR4/CXCL12 signaling pathway is a promising therapeutic option to refine radiotherapy.
癌细胞的放射抗性仍然是实现最大放疗效率的一个基本障碍。肿瘤异质性和不同基因型和生物学行为的不同细胞亚群的存在增加了根除所有致瘤细胞的难度。最近的证据表明，一种称为癌症干细胞（CSC）的独特肿瘤细胞群体参与了肿瘤的发生和复发，并且是肿瘤放射抗性的一个潜在原因。迫切需要确定调节放射抵抗的内在分子机制，特别是在 CSC 亚群中。趋化因子 C-X-C 基序受体 4（CXCR4）已被发现是各种类型癌症的预后标志物，参与趋化性、干细胞特性和耐药性。CXCR4 与其配体趋化因子 C-X-C 基序配体 12（CXCL12）的相互作用在调节肿瘤微环境、血管生成和 CSC 生态位方面发挥着重要作用。此外，CXCR4/CXCL12 信号通路的治疗抑制可使恶性细胞对常规抗癌治疗敏感。
在这篇综述中，我们总结了 CXCR4/CXCL12 轴在调节 CSC 特性、对放疗的肿瘤微环境反应、治疗抵抗和肿瘤复发中的作用。
鉴于最近的发现，抑制 CXCR4/CXCL12 信号通路是一种有前途的治疗选择，可以改进放疗。
