Matsumoto Kentaro, Hagiya Yuichiro, Endo Yoshio, Nakajima Motowo, Ishizuka Masahiro, Tanaka Tohru, Ogura Shun-ichiro
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Photodiagnosis Photodyn Ther. 2015 Mar;12(1):45-51. doi: 10.1016/j.pdpdt.2014.12.008. Epub 2015 Jan 5.
Currently, 5-aminolevulinic acid-based photodynamic diagnosis (ALA-PDD) is used to detect tumors during surgery and exploit tumor-specific accumulation of protoporphyrin IX (PpIX) after administration of ALA. In a recent study, we showed that the human ATP-binding cassette transporter ABCG2 plays a key role in the regulation of PpIX as a specific exporter. However, coproporphyrin III (CPIII) was also detected in urine after ALA administration in patients with tumor, indicating the presence of a CPIII transporter.
We used two lines of human gastric cancer cells to measure the ALA-induced porphyrin metabolism. Intracellular and extracellular porphyrin levels and expressions of transporter were determined.
In the present study, we showed that although ABCG2 did not transport CPIII, plasma membrane ABCB6 did. Moreover, under conditions of hypoxia, the expression of ABCB6 in plasma membrane was upregulated, resulting in increased extracellular CPIII concentrations.
These data indicate that the expression of ABCB6 in plasma membrane is important for porphyrin accumulation after ALA administration, including hypoxic conditions.
目前，基于5-氨基酮戊酸的光动力诊断（ALA-PDD）用于手术期间检测肿瘤，并利用ALA给药后原卟啉IX（PpIX）在肿瘤中的特异性蓄积。在最近的一项研究中，我们表明人类ATP结合盒转运蛋白ABCG2作为一种特异性转运体在PpIX的调节中起关键作用。然而，肿瘤患者给予ALA后尿液中也检测到了粪卟啉III（CPIII），这表明存在CPIII转运体。
我们使用两株人胃癌细胞系来测量ALA诱导的卟啉代谢。测定细胞内和细胞外卟啉水平以及转运体的表达。
在本研究中，我们表明虽然ABCG2不转运CPIII，但质膜ABCB6可以转运。此外，在缺氧条件下，质膜中ABCB6的表达上调，导致细胞外CPIII浓度增加。
这些数据表明，质膜中ABCB6的表达对于ALA给药后卟啉的蓄积很重要，包括在缺氧条件下。
