title: Effects of plasma membrane ABCB6 on 5-aminolevulinic acid (ALA)-induced porphyrin accumulation in vitro: tumor cell response to hypoxia.
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.
  
  
  CONCLUSIONS
  These data indicate that the expression of ABCB6 in plasma membrane is important for porphyrin accumulation after ALA administration, including hypoxic conditions.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 B47, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hagiya
authors.affiliation: Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Endo
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo 106-6020, Japan.
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo 106-6020, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishizuka
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo 106-6020, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: 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.
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Ogura
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D003306:Coproporphyrins / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C107991:ABCB6 protein, human; D018528:ATP-Binding Cassette Transporters; D003306:Coproporphyrins; D017319:Photosensitizing Agents; C026971:coproporphyrin III; D000622:Aminolevulinic Acid; D010100:Oxygen
keywords: 5-Aminolevulinic acid; ABCB6; Coproporphyrin; Hypoxia