5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models.
5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models.
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DOI：
10.1371/journal.pone.0249650
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Kataoka H
中科院分区：
文献类型：
--
作者：
Sasaki M;Tanaka M;Ichikawa H;Suzuki T;Nishie H;Ozeki K;Shimura T;Kubota E;Tanida S;Kataoka H
胃肠道间质瘤（GIST）的诊断使用传统的胃肠道内窥镜检查是困难的，因为这样的恶性肿瘤不能区分其他类型的粘膜下肿瘤。光动力学诊断（PDD）是基于肿瘤组织对光敏剂的优先吸收，以及在激光激发下通过荧光发射检测光敏剂。在这项研究中，我们研究了使用5-氨基乙酰丙酸（5-ALA）的PDD是否可用于GIST诊断，5-ALA是全球使用的标准光敏剂。5-ALA代谢为内源性荧光原卟啉IX（PpIX）。我们用流式细胞术和免疫荧光染色检测了PpIX在GIST-T1细胞中的积累。此外，我们建立了GIST-T1异种移植小鼠模型，并检查了PpIX在所得肿瘤中的积累。PpIX在GIST-T1细胞中积累，主要定位于溶酶体。在鼠异种移植肿瘤中也观察到PpIX积累。此外，肿瘤和正常组织可以区分由相对PpIX荧光。因此，我们的研究结果表明，PDD与5-ALA有很大的临床潜力，GIST的诊断。
Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.
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