Transcriptome analysis of human oral squamous cancer SAS cells as an early response after boron neutron capture therapy

Shoji Imamichi; Tasuku Ito; Ying Tong; Zhongming Gao; Yasuhito Arai; Hiroaki Fujimori; Lichao Chen; Yu Sanada; Satoshi Nakamura; Yasufumi Murakami; Masamichi Ishiai; Minoru Suzuki; Jun Itami; Hiroshi Igaki; Shinichiro Masunaga; Mitsuko Masutani

doi:10.1016/j.apradiso.2024.111648

Transcriptome analysis of human oral squamous cancer SAS cells as an early response after boron neutron capture therapy

Appl Radiat Isot. 2025 Jan 2:218:111648. doi: 10.1016/j.apradiso.2024.111648. Online ahead of print.

Authors

Shoji Imamichi¹, Tasuku Ito², Ying Tong³, Zhongming Gao⁴, Yasuhito Arai⁵, Hiroaki Fujimori⁶, Lichao Chen³, Yu Sanada⁷, Satoshi Nakamura⁸, Yasufumi Murakami⁹, Masamichi Ishiai¹⁰, Minoru Suzuki⁷, Jun Itami¹¹, Hiroshi Igaki¹¹, Shinichiro Masunaga⁷, Mitsuko Masutani¹²

Affiliations

¹ Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, 852-8523, Nagasaki, Japan; Central Radioisotope Division, National Cancer Center Research Institute, 104-0045, Tokyo, Japan; Division of BNCT, EPOC, National Cancer Center, Tokyo, Japan; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Japan; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, 104-0045, Tokyo, Japan.
² Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, 104-0045, Tokyo, Japan; Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
³ Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, 852-8523, Nagasaki, Japan; Central Radioisotope Division, National Cancer Center Research Institute, 104-0045, Tokyo, Japan.
⁴ Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, 852-8523, Nagasaki, Japan.
⁵ Division of Cancer Genomics, National Cancer Center Research Institute, 104-0045, Tokyo, Japan.
⁶ Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, 852-8523, Nagasaki, Japan; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, 104-0045, Tokyo, Japan.
⁷ Institute for Integrated Radiation and Nuclear Science, Kyoto University, Japan.
⁸ Division of BNCT, EPOC, National Cancer Center, Tokyo, Japan; Division of Radiation Safety and Quality Assurance, National Cancer Center Hospital, Tokyo, Japan.
⁹ Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
¹⁰ Central Radioisotope Division, National Cancer Center Research Institute, 104-0045, Tokyo, Japan; Division of BNCT, EPOC, National Cancer Center, Tokyo, Japan.
¹¹ Division of BNCT, EPOC, National Cancer Center, Tokyo, Japan; Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.
¹² Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, 852-8523, Nagasaki, Japan; Central Radioisotope Division, National Cancer Center Research Institute, 104-0045, Tokyo, Japan; Division of BNCT, EPOC, National Cancer Center, Tokyo, Japan; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, 104-0045, Tokyo, Japan. Electronic address: [email protected].

PMID: 39827644
DOI: 10.1016/j.apradiso.2024.111648

Abstract

Boron neutron capture therapy (BNCT) is based on nuclear reactions between thermal neutron and boron-10 preferentially distributed in the cancer cells. ¹⁰B-boronophenylalanine (BPA) is the approved drug for treatment of oral cancers for BNCT. However, the predictive biomarkers to evaluate therapeutic efficacy and side-effects have not been clarified yet. Here we performed comprehensive analysis of mRNA expression using human oral squamous carcinoma SAS cells after BPA-BNCT. The expression of particular mRNAs including inflammatory and immune-related responses and transcription factors, namely CSF2, ATF3, MAFB, PTGS2 and TNFAIP3 was increased 24 h after neutron irradiation of therapeutic dose of BPA-BNCT. NF-κB pathway genes were also activated after BNCT. The early increase of the gene product of CSF2 gene, granulocyte-macrophage colony stimulating factor (GM-CSF), in culture supernatant of SAS cells was observed by ELISA analysis after BPA-BNCT at a setting dose of 24 Gy-eq. The GM-CSF level was also increased after equivalent dose of gamma-ray and carbon beam irradiation. GM-CSF may be involved in local and systemic early responses of BNCT for particular types of cancer.

Keywords: BNCT; BPA; CSF2; GM-CSF; Transcriptome.