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Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary cancer therapy that involves boron administration and neutron irradiation. The nuclear reaction caused by the interaction of boron atom and neutron produces heavy particles with highly cytocidal effects and destruct tumor cells, which uptake the boron...

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Autores principales: Watanabe, Tsubasa, Sanada, Yu, Hattori, Yoshihide, Suzuki, Minoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855323/
https://www.ncbi.nlm.nih.gov/pubmed/36371738
http://dx.doi.org/10.1093/jrr/rrac077
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author Watanabe, Tsubasa
Sanada, Yu
Hattori, Yoshihide
Suzuki, Minoru
author_facet Watanabe, Tsubasa
Sanada, Yu
Hattori, Yoshihide
Suzuki, Minoru
author_sort Watanabe, Tsubasa
collection PubMed
description Boron neutron capture therapy (BNCT) is a binary cancer therapy that involves boron administration and neutron irradiation. The nuclear reaction caused by the interaction of boron atom and neutron produces heavy particles with highly cytocidal effects and destruct tumor cells, which uptake the boron drug. p-Boronophenylalanine (BPA), an amino acid derivative, is used in BNCT. Tumor cells with increased nutrient requirements take up more BPA than normal tissues via the enhanced expression of LAT1, an amino acid transporter. The current study aimed to assess the correlation between the expression of LAT1 and the uptake capacity of BPA using genetically modified LAT1-deficient/enhanced cell lines. We conducted an in vitro study, SCC7 tumor cells wherein LAT1 expression was altered using CRISPR/Cas9 were used to assess BPA uptake capacity. Data from The Cancer Genome Atlas (TCGA) were used to examine the expression status of LAT1 in human tumor tissues, the potential impact of LAT1 expression on cancer prognosis and the potential cancer indications for BPA-based BNCT. We discovered that the strength of LAT1 expression strongly affected the BPA uptake ability of tumor cells. Among the histologic types, squamous cell carcinomas express high levels of LAT1 regardless of the primary tumor site. The higher LAT1 expression in tumors was associated with a higher expression of cell proliferation markers and poorer patient prognosis. Considering that BPA concentrate more in tumors with high LAT1 expression, the results suggest that BNCT is effective for cancers having poor prognosis with higher proliferative potential and nutritional requirements.
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spelling pubmed-98553232023-01-23 Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy Watanabe, Tsubasa Sanada, Yu Hattori, Yoshihide Suzuki, Minoru J Radiat Res Regular paper Boron neutron capture therapy (BNCT) is a binary cancer therapy that involves boron administration and neutron irradiation. The nuclear reaction caused by the interaction of boron atom and neutron produces heavy particles with highly cytocidal effects and destruct tumor cells, which uptake the boron drug. p-Boronophenylalanine (BPA), an amino acid derivative, is used in BNCT. Tumor cells with increased nutrient requirements take up more BPA than normal tissues via the enhanced expression of LAT1, an amino acid transporter. The current study aimed to assess the correlation between the expression of LAT1 and the uptake capacity of BPA using genetically modified LAT1-deficient/enhanced cell lines. We conducted an in vitro study, SCC7 tumor cells wherein LAT1 expression was altered using CRISPR/Cas9 were used to assess BPA uptake capacity. Data from The Cancer Genome Atlas (TCGA) were used to examine the expression status of LAT1 in human tumor tissues, the potential impact of LAT1 expression on cancer prognosis and the potential cancer indications for BPA-based BNCT. We discovered that the strength of LAT1 expression strongly affected the BPA uptake ability of tumor cells. Among the histologic types, squamous cell carcinomas express high levels of LAT1 regardless of the primary tumor site. The higher LAT1 expression in tumors was associated with a higher expression of cell proliferation markers and poorer patient prognosis. Considering that BPA concentrate more in tumors with high LAT1 expression, the results suggest that BNCT is effective for cancers having poor prognosis with higher proliferative potential and nutritional requirements. Oxford University Press 2022-11-14 /pmc/articles/PMC9855323/ /pubmed/36371738 http://dx.doi.org/10.1093/jrr/rrac077 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular paper
Watanabe, Tsubasa
Sanada, Yu
Hattori, Yoshihide
Suzuki, Minoru
Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title_full Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title_fullStr Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title_full_unstemmed Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title_short Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy
title_sort correlation between the expression of lat1 in cancer cells and the potential efficacy of boron neutron capture therapy
topic Regular paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855323/
https://www.ncbi.nlm.nih.gov/pubmed/36371738
http://dx.doi.org/10.1093/jrr/rrac077
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