Kentaro Matsumoto1, Yuichiro Hagiya1, Yoshio Endo2, Motowo Nakajima3, Masahiro Ishizuka3, Tohru Tanaka3, Shun-ichiro Ogura4. 1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. 2. Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. 3. SBI Pharmaceuticals Co., Ltd., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo 106-6020, Japan. 4. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. Electronic address: sogura@bio.titech.ac.jp.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These data indicate that the expression of ABCB6 in plasma membrane is important for porphyrin accumulation after ALA administration, including hypoxic conditions.
BACKGROUND: 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. METHODS: We used two lines of humangastric cancer cells to measure the ALA-induced porphyrin metabolism. Intracellular and extracellular porphyrin levels and expressions of transporter were determined. RESULTS: 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. CONCLUSION: These data indicate that the expression of ABCB6 in plasma membrane is important for porphyrin accumulation after ALA administration, including hypoxic conditions.
Authors: Giuseppe Palmieri; Fabio Cofano; Luca Francesco Salvati; Matteo Monticelli; Pietro Zeppa; Giuseppe Di Perna; Antonio Melcarne; Roberto Altieri; Giuseppe La Rocca; Giovanni Sabatino; Giuseppe Maria Barbagallo; Fulvio Tartara; Francesco Zenga; Diego Garbossa Journal: Technol Cancer Res Treat Date: 2021 Jan-Dec
Authors: Elizabeth S Egan; Michael P Weekes; Usheer Kanjee; Jale Manzo; Ashwin Srinivasan; Christine Lomas-Francis; Connie Westhoff; Junko Takahashi; Mitsunobu Tanaka; Seishi Watanabe; Carlo Brugnara; Steven P Gygi; Yoshihiko Tani; Manoj T Duraisingh Journal: Commun Biol Date: 2018-05-03