Understanding the cellular origin and progression of esophageal cancer using esophageal organoids.
Understanding the cellular origin and progression of esophageal cancer using esophageal organoids.
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DOI：
10.1016/j.canlet.2021.03.031
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发表时间：
2021-07-01
期刊：
影响因子：
9.7
通讯作者：
Nakagawa H
中科院分区：
文献类型：
--
作者：
Sachdeva UM;Shimonosono M;Flashner S;Cruz-Acuña R;Gabre JT;Nakagawa H
三维（3D）类器官是一种新的工具，模拟上皮细胞生物学和人类食管疾病。3D类器官培养系统已被用于研究食管癌的病理生物学，包括鳞状细胞癌和腺癌。用于研究食管发育和良性食管疾病的其他基于类器官的方法为食管角质形成细胞分化和粘膜再生提供了关键见解。这些研究对食管癌干细胞的鉴定以及通过诱导分化途径阻止恶性进展的潜力具有意义。来自人体组织样本的患者源性类器官（PDO）允许食管癌的独特和忠实的体外建模，并为研究个性化药物和靶向治疗方法以及了解治疗抗性和复发性疾病的新模型提供了令人兴奋的平台。未来的发展方向包括使用PDO进行高通量基因组筛选，以及通过与免疫和基质细胞以及新型细胞外基质复合物共培养来研究肿瘤微环境相互作用。
Three-dimensional (3D) organoids are a novel tool to model epithelial cell biology and human diseases of the esophagus. 3D organoid culture systems have been utilized to investigate the pathobiology of esophageal cancer, including both squamous cell carcinoma and adenocarcinoma. Additional organoid-based approaches for study of esophageal development and benign esophageal diseases have provided key insights into esophageal keratinocyte differentiation and mucosal regeneration. These investigations have implications for the identification of esophageal cancer stem cells, as well as the potential to halt malignant progression through induction of differentiation pathways. Patient-derived organoids (PDOs) from human tissue samples allow for unique and faithful in vitro modeling of esophageal cancers, and provide an exciting platform for investigation into personalized medicine and targeted treatment approaches, as well as new models for understanding therapy resistance and recurrent disease. Future directions include high-throughput genomic screening using PDOs, and study of tumor-microenvironmental interactions through co-culture with immune and stromal cells and novel extracellular matrix complexes.
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