Kinoshita Hidehito, Kanda Tsutomu, Takata Tomoaki, Sugihara Takaaki, Mae Yukari, Yamashita Taro, Onoyama Takumi, Takeda Yohei, Isomoto Hajime
Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
Yonago Acta Med. 2020 Jun 12;63(3):154-162. doi: 10.33160/yam.2020.08.003. eCollection 2020 Aug.
The 5-aminolevulinic acid (ALA)-based photodynamic diagnosis is based on the accumulation of photosensitizing protoporphyrin IX in the tumor after ALA administration. However, the mechanisms connecting exogenous ALA and tumor fluorescence in pancreatic cancer remain unclear. We aimed to elucidate the mechanism underlying the ALA-induced fluorescent.
Human pancreatic duct epithelial cells (hPDECs) and pancreatic cancer cell lines were used. The expressions of ALA-associated enzymes and membrane transporters in these cell lines were investigated. ALA-induced fluorescence was also investigated.
The expression of oligopeptide transporter-1 (PEPT-1), through which ALA is absorbed, was significantly higher in AsPC-1 cells and lower in MIA PaCa-2 cells than in hPDECs. AsPC-1 cells showed rapid and intense fluorescence after ALA administration, and that was attenuated by PEPT-1 inhibition. ALA-induced fluorescence was not sufficiently strong in MIA PaCa-2 cells to distinguish the cells from hPDECs.
We revealed the association of PEPT-1 with ALA-induced fluorescence. Cancers expressing PEPT-1 could be easily distinguished by this technique from normal cells. These findings help develop novel diagnostic modalities for pancreatic cancer.
基于5-氨基乙酰丙酸(ALA)的光动力诊断是基于给予ALA后肿瘤中光敏原卟啉IX的积累。然而,胰腺癌中外源性ALA与肿瘤荧光之间的联系机制仍不清楚。我们旨在阐明ALA诱导荧光的潜在机制。
使用人胰腺导管上皮细胞(hPDEC)和胰腺癌细胞系。研究了这些细胞系中与ALA相关的酶和膜转运蛋白的表达。还研究了ALA诱导的荧光。
吸收ALA的寡肽转运蛋白1(PEPT-1)在AsPC-1细胞中的表达显著高于hPDEC,在MIA PaCa-2细胞中的表达低于hPDEC。给予ALA后,AsPC-1细胞显示出快速而强烈的荧光,并且这种荧光被PEPT-1抑制所减弱。在MIA PaCa-2细胞中,ALA诱导的荧光不够强,无法将细胞与hPDEC区分开来。
我们揭示了PEPT-1与ALA诱导的荧光之间的关联。通过该技术,表达PEPT-1的癌症可以很容易地与正常细胞区分开来。这些发现有助于开发胰腺癌的新型诊断方法。