Lammert Anne, Affolter Annette, Gvaramia David, Heid Jonas, Jungbauer Frederic, Scherl Claudia, Tenschert Esther, Rotter Nicole, Willett Nicola, Kern Johann
Klinik für Hals-Nasen-Ohren-Heilkunde, Kopf- und Halschirurgie, Fakultät Mannheim, Universität Heidelberg.
Laryngorhinootologie. 2021 Jan;100(1):23-29. doi: 10.1055/a-1260-3054. Epub 2021 Jan 5.
An increasing amount of evidence suggests the existence of a stem cell-like population in head and neck squamous cell carcinoma (HNSCC). These cells have been termed cancer stem cells (CSC) due to the shared properties with somatic stem cells, such as the ability to self-renew and differentiate. Furthermore, the CSC are thought to be resistant to antineoplastic treatments and are therefore clinically relevant. As with somatic stem cells, CSC are thought to reside in a specialized supportive microenvironment, called the stem cell niche. One possible strategy to target the CSC could be through affecting functions of the stem cell niche.Stromal cell-derived factor-1 (SDF-1) is a multifunctional cytokine, which is secreted by e. g. stromal cells within the niche. SDF-1 is known to be the major regulator of stem cell trafficking between the niche and the peripheral vascular system. It elicits the chemotactic activity through interaction with a transmembrane receptor CXCR4, expressed by CSC. The SDF-1-CXCR4-axis is thought to play a crucial role in the interaction between CSC and their supportive cells in the tumor niche. A better understanding of these interactions could help in gaining further insight into the pathophysiology of progression/recurrence of malignant diseases and aid in finding new strategies for therapy.Specialized cell culture models are of advantage for deciphering the mechanisms of interaction between CSC and their niche. We anticipate that the recent technological advancements in bioprinting and the development of complex 3D cell culture model systems will contribute to our understanding of these mechanisms and to the establishment of individualized therapies.Here were provide an overview of the current knowledge on the CSC-tumor stem cell niche interactions in HNSCC with a focus on the SDF-1-CXCR4 axis.
越来越多的证据表明，头颈部鳞状细胞癌（HNSCC）中存在类似干细胞的细胞群。由于这些细胞与体细胞干细胞具有共同特性，如自我更新和分化能力，因此被称为癌症干细胞（CSC）。此外，癌症干细胞被认为对抗肿瘤治疗具有抗性，因此具有临床相关性。与体细胞干细胞一样，癌症干细胞被认为存在于一个特殊的支持性微环境中，称为干细胞龛。靶向癌症干细胞的一种可能策略是通过影响干细胞龛的功能。基质细胞衍生因子-1（SDF-1）是一种多功能细胞因子，例如由龛内的基质细胞分泌。已知SDF-1是干细胞在龛与外周血管系统之间迁移的主要调节因子。它通过与癌症干细胞表达的跨膜受体CXCR4相互作用引发趋化活性。SDF-1-CXCR4轴被认为在肿瘤龛中癌症干细胞与其支持细胞之间的相互作用中起关键作用。更好地理解这些相互作用有助于进一步深入了解恶性疾病进展/复发的病理生理学，并有助于找到新的治疗策略。专门的细胞培养模型有助于解读癌症干细胞与其龛之间的相互作用机制。我们预计，生物打印方面的最新技术进展以及复杂3D细胞培养模型系统的开发将有助于我们理解这些机制，并有助于建立个性化疗法。在此，我们概述了目前关于头颈部鳞状细胞癌中癌症干细胞-肿瘤干细胞龛相互作用的知识，重点是SDF-1-CXCR4轴。
