RRC ID 54812
Author Omoto K, Matsuda R, Nakai Y, Tatsumi Y, Nakazawa T, Tanaka Y, Shida Y, Murakami T, Nishimura F, Nakagawa I, Motoyama Y, Nakamura M, Fujimoto K, Hiroyuki N.
Title Expression of peptide transporter 1 has a positive correlation in protoporphyrin IX accumulation induced by 5-aminolevulinic acid with photodynamic detection of non-small cell lung cancer and metastatic brain tumor specimens originating from non-small cell lung cancer.
Journal Photodiagnosis Photodyn Ther
Abstract BACKGROUND:Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors.
METHODS:Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors.
RESULTS:A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009).
CONCLUSION:Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.
Volume 25
Pages 309-316
Published 2019-3
DOI 10.1016/j.pdpdt.2019.01.009
PII S1572-1000(18)30329-6
PMID 30639584
MeSH ATP Binding Cassette Transporter, Subfamily G, Member 2 / biosynthesis Aminolevulinic Acid / pharmacology* Blotting, Western Brain Neoplasms / drug therapy Brain Neoplasms / secondary Carcinoma, Non-Small-Cell Lung / drug therapy Carcinoma, Non-Small-Cell Lung / pathology Cell Line, Tumor Ferrochelatase / biosynthesis Heme Oxygenase-1 / biosynthesis Humans Lung Neoplasms / drug therapy Lung Neoplasms / pathology Neoplasm Metastasis Peptide Transporter 1 / biosynthesis* Photochemotherapy / methods* Protoporphyrins / metabolism* Real-Time Polymerase Chain Reaction Spectrometry, Fluorescence Uroporphyrinogens / biosynthesis
IF 2.895
Resource
Human and Animal Cells LC-1/sq(RCB0455) RERF-LC-AI(RCB0444) HLC-1(RCB0083) RERF-LC-KJ(RCB1313)