5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids
5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids
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DOI：
10.1016/j.suronc.2020.10.011
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发表时间：
2020-12-01
影响因子：
2.3
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
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作者：
Fujiwara, Hiroaki;Takahara, Naminatsu;Koike, Kazuhiko
背景：胆管细胞癌(CCA)病变范围的准确诊断在临床实践中往往是困难的。传统的术前影像或内窥镜检查的诊断率有时不足以评估颈总动脉的纵向扩散。在这里，我们研究了5-氨基乙酰丙酸(5-ALA)在CCA术前或术中诊断中的作用，使用的是患者来源的有机物质。结果：从不同患者体内构建的CCA有机类化合物与非肿瘤类有机化合物的单层结构相比，具有不同的形态特征，并具有在免疫缺陷小鼠体内形成皮下肿瘤的能力。CCA有机化合物表现出非常高的光动力活性，这是因为与非肿瘤有机化合物相比，作为5-ALA代谢产物的原卟啉IX积累更多(分别为40-71%和4%)。重要的是，在CCA患者中，癌细胞特异性的高光动力活性区分了起源于胆管狭窄病变和非狭窄病变的器质性物质。高光动力活性不依赖于血红素生物合成基因的表达谱。结论：基于5-ALA的光动力活性可用于CCA与非肿瘤组织的鉴别诊断。
Background: Accurate diagnosis of the disease extension of cholangiocarcinoma (CCA) is often difficult in clinical practice. The diagnostic yield of conventional pre-operative imaging or endoscopic procedures is sometimes insufficient for the evaluation of longitudinal spreading of CCA. Here we investigated the usefulness of 5-aminolevulinic acid (5-ALA) for the pre- or intra-operative diagnosis of CCA, using patient-derived organoids.Methods: Four CCA- and two adjacent tissue-derived organoids were established. After 5-ALA treatment, we assessed their photodynamic activity using fluorescence microscopy.Results: CCA organoids established from different patients showed diverse morphology in contrast to monolayer structures of non-tumor organoids, and had the ability to form subcutaneous tumors in immunodeficient mice. CCA organoids demonstrated remarkably high photodynamic activity based on higher accumulation of protoporphyrin IX as a metabolite of 5-ALA compared to non-tumor organoids (40-71% vs. < 4%, respectively). Importantly, cancer cell-specific high photodynamic activity distinguished the organoids originated from biliary stenotic lesions from those of non-stenotic lesions in a CCA patient. The high photodynamic activity did not depend on the expression profile of heme biosynthesis genes.Conclusions: Distinct 5-ALA-based photodynamic activity could have diagnostic potential for the discrimination of CCA from non-tumor tissues.