Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy
Boron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we...
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2022-03-01
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| author | Shoji Imamichi Lichao Chen Tasuku Ito Ying Tong Takae Onodera Yuka Sasaki Satoshi Nakamura PierLuigi Mauri Yu Sanada Hiroshi Igaki Yasufumi Murakami Minoru Suzuki Jun Itami Shinichiro Masunaga Mitsuko Masutani |
| author_facet | Shoji Imamichi Lichao Chen Tasuku Ito Ying Tong Takae Onodera Yuka Sasaki Satoshi Nakamura PierLuigi Mauri Yu Sanada Hiroshi Igaki Yasufumi Murakami Minoru Suzuki Jun Itami Shinichiro Masunaga Mitsuko Masutani |
| author_sort | Shoji Imamichi |
| collection | DOAJ |
| description | Boron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we aimed to investigate HMGB1 as a biomarker for BNCT response, by examining the early responses of tumor cells to <sup>10</sup>B-boronophenylalanine (BPA)-based BNCT in the Kyoto University Nuclear Reactor. Extracellular HMGB1 release was significantly increased in human squamous carcinoma SAS and melanoma A375 cells 24 h after neutron irradiation but not after γ-irradiation. At 3 days post-BPA-based BNCT irradiation in a SAS xenograft mouse model, plasma HMGB1 levels were higher than those in the non-irradiation control, and HMGB1 was detected in both nuclei and cytoplasm in tumor cells. Additionally, increased plasma HMGB1 levels post-BNCT irradiation were detected even when tumors decreased in size. Collectively, these results indicate that the extracellular HMGB1 release occurs at an early stage and is persistent when tumors are reduced in size; therefore, it is a potential biomarker for evaluating the therapeutic response during BNCT. |
| first_indexed | 2024-03-09T13:50:00Z |
| format | Article |
| id | doaj.art-4b2cbec1514d450baebe69251cdafab9 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T13:50:00Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Biology |
| spelling | doaj.art-4b2cbec1514d450baebe69251cdafab92023-11-30T20:51:57ZengMDPI AGBiology2079-77372022-03-0111342010.3390/biology11030420Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture TherapyShoji Imamichi0Lichao Chen1Tasuku Ito2Ying Tong3Takae Onodera4Yuka Sasaki5Satoshi Nakamura6PierLuigi Mauri7Yu Sanada8Hiroshi Igaki9Yasufumi Murakami10Minoru Suzuki11Jun Itami12Shinichiro Masunaga13Mitsuko Masutani14Department of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanDepartment of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanLab of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo 104-0045, JapanDepartment of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanDepartment of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanDepartment of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanDivision of BNCT, EPOC, National Cancer Center, Tokyo 104-0045, JapanClinical Proteomics Laboratory, Institute of Biomedical Technologies, National Research Council, 93-20054 Milan, ItalyInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori 590-0494, JapanDivision of BNCT, EPOC, National Cancer Center, Tokyo 104-0045, JapanDepartment of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori 590-0494, JapanDivision of BNCT, EPOC, National Cancer Center, Tokyo 104-0045, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Kumatori 590-0494, JapanDepartment of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, JapanBoron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we aimed to investigate HMGB1 as a biomarker for BNCT response, by examining the early responses of tumor cells to <sup>10</sup>B-boronophenylalanine (BPA)-based BNCT in the Kyoto University Nuclear Reactor. Extracellular HMGB1 release was significantly increased in human squamous carcinoma SAS and melanoma A375 cells 24 h after neutron irradiation but not after γ-irradiation. At 3 days post-BPA-based BNCT irradiation in a SAS xenograft mouse model, plasma HMGB1 levels were higher than those in the non-irradiation control, and HMGB1 was detected in both nuclei and cytoplasm in tumor cells. Additionally, increased plasma HMGB1 levels post-BNCT irradiation were detected even when tumors decreased in size. Collectively, these results indicate that the extracellular HMGB1 release occurs at an early stage and is persistent when tumors are reduced in size; therefore, it is a potential biomarker for evaluating the therapeutic response during BNCT.https://www.mdpi.com/2079-7737/11/3/420<sup>10</sup>B-boronophenylalanine (BPA)boron neutron capture therapy (BNCT)boron neutron capture reaction (BNCR)high mobility group box 1 (HMGB1) |
| spellingShingle | Shoji Imamichi Lichao Chen Tasuku Ito Ying Tong Takae Onodera Yuka Sasaki Satoshi Nakamura PierLuigi Mauri Yu Sanada Hiroshi Igaki Yasufumi Murakami Minoru Suzuki Jun Itami Shinichiro Masunaga Mitsuko Masutani Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy Biology <sup>10</sup>B-boronophenylalanine (BPA) boron neutron capture therapy (BNCT) boron neutron capture reaction (BNCR) high mobility group box 1 (HMGB1) |
| title | Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy |
| title_full | Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy |
| title_fullStr | Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy |
| title_full_unstemmed | Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy |
| title_short | Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy |
| title_sort | extracellular release of hmgb1 as an early potential biomarker for the therapeutic response in a xenograft model of boron neutron capture therapy |
| topic | <sup>10</sup>B-boronophenylalanine (BPA) boron neutron capture therapy (BNCT) boron neutron capture reaction (BNCR) high mobility group box 1 (HMGB1) |
| url | https://www.mdpi.com/2079-7737/11/3/420 |
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