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Investigation of the Role and Dynamics of Yolk Sac–Derived Tissue-Resident Macrophages in Oral Squamous Cell Carcinoma

Research Project

Project/Area Number 21K17089
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionOkayama University

Principal Investigator

Kawai Hotaka  岡山大学, 医歯薬学域, 研究准教授 (10803687)

Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords扁平上皮癌 / 腫瘍微小環境 / 骨髄由来細胞 / 口腔扁平上皮癌 / 骨髄移植 / TAM / 組織マクロファージ / 口腔癌 / 頭頸部癌 / 癌微小環境 / 癌免疫
Outline of Research at the Start

本研究は、Cx3cr1レポーターマウスを用いて組織マクロファージを可視化し、口腔癌の浸潤や転移における同細胞の役割を検討する。申請者は既に腫瘍転移組織において組織マクロファージの関与を示唆する結果を得ており、研究の実現可能性は極めて高い。本研究により腫瘍内の組織マクロファージの表面マーカーや発現因子が明らかになれば、腫瘍の浸潤や転移に重要な組織マクロファージの性格が理解され、組織マクロファージを標的とした分子標的治療など新たな研究領域に発展する可能性がある。

Outline of Final Research Achievements

In this study, we used Cx3cr1-reporter and GFP bone marrow transplantation mice to clarify the roles of tissue-resident macrophages in oral squamous cell carcinoma. Tissue-resident macrophages labeled with tdTomato showed distinct localization and behavior compared to bone marrow-derived macrophages, particularly contributing to tumor progression in highly malignant tumors. FACS and multiplex immunostaining further revealed functional and marker differences. These findings provide novel insight into TAM heterogeneity and may lead to new strategies in cancer immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

本研究では、口腔扁平上皮癌における組織マクロファージの動態と役割を明らかにし、骨髄由来マクロファージとは異なる腫瘍促進的機能を有することを示した。これにより、腫瘍免疫におけるマクロファージの由来別機能が解明され、TAMの新たな分類・標的化が可能となる。将来的には、組織マクロファージを標的とした分子標的治療や免疫療法の開発につながることが期待され、難治性癌に対する新たな治療戦略の構築に資する重要な知見を提供する。

Report

(5 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (29 results)

All 2024 2023 2022 2021

All Journal Article (25 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 25 results,  Open Access: 24 results) Presentation (4 results)

  • [Journal Article] Double-faced CX3CL1 enhances lymphangiogenesis-dependent metastasis in an aggressive subclone of oral squamous cell carcinoma2024

    • Author(s)
      Eain HS, Kawai H, Nakayama M, Oo MW, Ohara T, Fukuhara Y, Takabatake K, Shan Q, Soe Y, Ono K, Nakano K, Mizukawa N, Iida S, Nagatsuka H.
    • Journal Title

      JCI Insight.

      Volume: 9(10) Issue: 10 Pages: 174618-174618

    • DOI

      10.1172/jci.insight.174618

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer2024

    • Author(s)
      Saori Yoshida, Hotaka Kawai, Yamin Soe, Htoo Shwe Eain, Sho Sanou, Kiyofumi Takabatake, Yohei Takeshita, Miki Hisatomi, Hitoshi Nagatsuka, Junichi Asaumi, Yoshinobu Yanagi
    • Journal Title

      Cancers

      Volume: 16 Issue: 13 Pages: 2326-2326

    • DOI

      10.3390/cancers16132326

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Scaffold Geometrical Structure on Macrophage Polarization during Bone Regeneration Using Honeycomb Tricalcium Phosphate2024

    • Author(s)
      Takabatake Kiyofumi、Tsujigiwa Hidetsugu、Nakano Keisuke、Chang Anqi、Piao Tianyan、Inada Yasunori、Arashima Takuma、Morimatsu Ayumi、Tanaka Ayumi、Kawai Hotaka、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 17 Issue: 16 Pages: 4108-4108

    • DOI

      10.3390/ma17164108

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab11 suppresses head and neck carcinoma by regulating EGFR and EpCAM exosome secretion2024

    • Author(s)
      Yoshida Kunihiro、Htike Kaung、Eguchi Takanori、Kawai Hotaka、Eain Htoo Shwe、Tran Manh Tien、Sogawa Chiharu、Umemori Koki、Ogawa Tatsuo、Kanemoto Hideka、Ono Kisho、Nagatsuka Hitoshi、Sasaki Akira、Ibaragi Soichiro、Okamoto Kuniaki
    • Journal Title

      Journal of Oral Biosciences

      Volume: 66 Issue: 1 Pages: 205-216

    • DOI

      10.1016/j.job.2023.11.007

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiplex Immunostaining Method to Distinguish HSP Isoforms in Cancer Tissue Specimens2023

    • Author(s)
      Kawai Hotaka、Ono Kisho、Eguchi Takanori
    • Journal Title

      Inteck Open

      Volume: 1 Pages: 281-291

    • DOI

      10.1007/978-1-0716-3342-7_21

    • ISBN
      9781071633410, 9781071633427
    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Artificial Scaffold for Bone Marrow Regeneration: Honeycomb Tricalcium Phosphate2023

    • Author(s)
      Inada Yasunori、Takabatake Kiyofumi、Tsujigiwa Hidetsugu、Nakano Keisuke、Shan Qiusheng、Piao Tianyan、Chang Anqi、Kawai Hotaka、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 16 Issue: 4 Pages: 1393-1393

    • DOI

      10.3390/ma16041393

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists2023

    • Author(s)
      Sukegawa Shintaro、Ono Sawako、Tanaka Futa、Inoue Yuta、Hara Takeshi、Yoshii Kazumasa、Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Katsumitsu Shimada、Nakai Fumi、Nakai Yasuhiro、Miyazaki Ryo、Murakami Satoshi、Nagatsuka Hitoshi、Miyake Minoru
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41598-023-38343-y

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enzyme‐Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem Cells2023

    • Author(s)
      Kawai Hotaka、Oo May Wathone、Takabatake Kiyofumi、Tosa Ikue、Soe Yamin、Eain Htoo Shwe、Sanou Sho、Fushimi Shigeko、Sukegawa Shintaro、Nakano Keisuke、Takeshi Takarada、Nagatsuka Hitoshi
    • Journal Title

      JBMR Plus

      Volume: 7 Issue: 3 Pages: 1-10

    • DOI

      10.1002/jbm4.10722

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma2023

    • Author(s)
      Umemori Koki、Ono Kisho、Eguchi Takanori、Kawai Hotaka、Nakamura Tomoya、Ogawa Tatsuo、Yoshida Kunihiro、Kanemoto Hideka、Sato Kohei、Obata Kyoichi、Ryumon Shoji、Yutori Hirokazu、Katase Naoki、Okui Tatsuo、Nagatsuka Hitoshi、Ibaragi Soichiro
    • Journal Title

      Oral Oncology

      Volume: 142 Pages: 106433-106433

    • DOI

      10.1016/j.oraloncology.2023.106433

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A histological study of the adult ligamentum arteriosum: Novel findings with application to a patent ductus arteriosus2023

    • Author(s)
      Iwanaga Joe、Choudhury Humza、Yu Aaron、Matsuo Katsuhisa、Kawai Hotaka、Han Aya、Tabira Yoko、Saga Tsuyoshi、Watanabe Koichi、Loukas Marios、Tubbs R. Shane
    • Journal Title

      Clinical Anatomy

      Volume: 37 Issue: 1 Pages: 140-146

    • DOI

      10.1002/ca.24122

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCAND1 Reverses Epithelial-to-Mesenchymal Transition (EMT) and Suppresses Prostate Cancer Growth and Migration2022

    • Author(s)
      Eguchi Takanori、Csizmadia Eva、Kawai Hotaka、Sheta Mona、Yoshida Kunihiro、Prince Thomas L.、Wegiel Barbara、Calderwood Stuart K.
    • Journal Title

      Cells

      Volume: 11 Issue: 24 Pages: 3993-3993

    • DOI

      10.3390/cells11243993

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment2022

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Takabatake Kiyofumi、Tomida Shuta、Eguchi Takanori、Ono Kisho、Shan Qiusheng、Ohara Toshiaki、Yoshida Saori、Omori Haruka、Sukegawa Shintaro、Nakano Keisuke、Okamoto Kuniaki、Sasaki Akira、Nagatsuka Hitoshi
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1172/jci.insight.148960

    • NAID

      120007186650

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma2022

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Eain Htoo Shwe、Soe Yamin、Takabatake Kiyofumi、Sanou Sho、Shan Qiusheng、Inada Yasunori、Fujii Masae、Fukuhara Yoko、Wang Ziyi、Sukegawa Shintaro、Ono Mitsuaki、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 11 Pages: 2729-2729

    • DOI

      10.3390/biomedicines10112729

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy2022

    • Author(s)
      Nakata Eiji、Kawai Hotaka、Fujiwara Tomohiro、Kunisada Toshiyuki、Inoue Hirofumi、Futagawa Mashu、Katayama Haruyoshi、Itano Takuto、Ozaki Toshifumi
    • Journal Title

      Oncology Letters

      Volume: 24 Issue: 3 Pages: 319-319

    • DOI

      10.3892/ol.2022.13439

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.2021

    • Author(s)
      Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki
    • Journal Title

      Biochim Biophys Acta - Molecular Basis of Disease

      Volume: 1867 Issue: 11 Pages: 166236-166236

    • DOI

      10.1016/j.bbadis.2021.166236

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preparation of Absorption-Resistant Hard Tissue Using Dental Pulp-Derived Cells and Honeycomb Tricalcium Phosphate2021

    • Author(s)
      Takabatake Kiyofumi、Nakano Keisuke、Kawai Hotaka、Inada Yasunori、Sukegawa Shintaro、Qiusheng Shan、Fushimi Shigeko、Tsujigiwa Hidetsugu、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 14 Issue: 12 Pages: 3409-3409

    • DOI

      10.3390/ma14123409

    • NAID

      120007099350

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma2021

    • Author(s)
      Omori Haruka、Shan Qiusheng、Takabatake Kiyofumi、Nakano Keisuke、Kawai Hotaka、Sukegawa Shintaro、Tsujigiwa Hidetsugu、Nagatsuka Hitoshi
    • Journal Title

      Cancers

      Volume: 13 Issue: 14 Pages: 3491-3491

    • DOI

      10.3390/cancers13143491

    • NAID

      120007126502

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma2021

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Omori Haruka、Kawai Hotaka、Oo May、Nakano Keisuke、Ibaragi Soichiro、Sasaki Akira、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Oncology

      Volume: 59 Issue: 3 Pages: 1-10

    • DOI

      10.3892/ijo.2021.5252

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Patient Clinical Variables in Osteoporosis Classification Using Hip X-rays in Deep Learning Analysis2021

    • Author(s)
      Yamamoto Norio、Sukegawa Shintaro、Yamashita Kazutaka、Manabe Masaki、Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Ozaki Toshifumi、Kawasaki Keisuke、Nagatsuka Hitoshi、Furuki Yoshihiko、Yorifuji Takashi
    • Journal Title

      Medicina

      Volume: 57 Issue: 8 Pages: 846-846

    • DOI

      10.3390/medicina57080846

    • NAID

      120007146053

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion2021

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Takabatake Kiyofumi、Shan Qiusheng、Eain Htoo Shwe、Sukegawa Shintaro、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Cancers

      Volume: 14 Issue: 1 Pages: 137-137

    • DOI

      10.3390/cancers14010137

    • NAID

      120007185107

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP2021

    • Author(s)
      Takabatake Kiyofumi、Tsujigiwa Hidetsugu、Yoshida Aki、Furumatsu Takayuki、Kawai Hotaka、Oo May Wathone、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 14 Issue: 23 Pages: 7225-7225

    • DOI

      10.3390/ma14237225

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process2021

    • Author(s)
      Kawai Hotaka、Oo May Wathone、Tsujigiwa Hidetsugu、Nakano Keisuke、Takabatake Kiyofumi、Sukegawa Shintaro、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Medical Sciences

      Volume: 18 Issue: 8 Pages: 1824-1830

    • DOI

      10.7150/ijms.51946

    • NAID

      120007019114

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological Effects of Bioresorbable Materials in Alveolar Ridge Augmentation: Comparison of Early and Slow Resorbing Osteosynthesis Materials2021

    • Author(s)
      Kawai Hotaka、Sukegawa Shintaro、Nakano Keisuke、Takabatake Kiyofumi、Ono Sawako、Nagatsuka Hitoshi、Furuki Yoshihiko
    • Journal Title

      Materials

      Volume: 14 Issue: 12 Pages: 3286-3286

    • DOI

      10.3390/ma14123286

    • NAID

      120007099352

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multi-Task Deep Learning Model for Classification of Dental Implant Brand and Treatment Stage Using Dental Panoramic Radiograph Images2021

    • Author(s)
      Sukegawa Shintaro、Yoshii Kazumasa、Hara Takeshi、Matsuyama Tamamo、Yamashita Katsusuke、Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Nagatsuka Hitoshi、Furuki Yoshihiko
    • Journal Title

      Biomolecules

      Volume: 11 Issue: 6 Pages: 815-815

    • DOI

      10.3390/biom11060815

    • NAID

      120007099342

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic contrast?enhanced MRI as a predictor of programmed death ligand?1 expression in patients with oral squamous cell carcinoma2021

    • Author(s)
      Tekiki Nouha、Fujita Mariko、Okui Tatsuo、Kawai Hotaka、Oo May、Kawazu Toshiyuki、Hisatomi Miki、Okada Shunsuke、Takeshita Yohei、Barham Majd、Nagatsuka Hitoshi、Yanagi Yoshinobu、Asaumi Jun-Ichi
    • Journal Title

      Oncology Letters

      Volume: 22 Issue: 5

    • DOI

      10.3892/ol.2021.13039

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨髄由来間葉系幹細胞の新規採取技術および骨髄由来間葉系幹細胞移植法の確立2023

    • Author(s)
      河合 穂高,メイ ワト ウ,.高畠 清文,佐能 彰,中野 敬介,宝田 剛,長塚 仁
    • Organizer
      第77回NPO法人日本口腔科学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] 口腔癌における CX3CL1 とリンパ節転移の関係2023

    • Author(s)
      河合 穂高、トゥ シュ エイン、中山 真彰、大原 利章、長塚 仁
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Research-status Report
  • [Presentation] CCL2-CCR2 axisを介した癌関連線維芽細胞による骨髄由来細胞の動員2021

    • Author(s)
      河合 穂高,、メイワトウ、高畠 清文、大森 悠加、中野 敬介、長塚 仁
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 癌微小環境における口腔癌間質細胞と骨髄由来細胞の 関係性について2021

    • Author(s)
      河合 穂高、 メイ ワト ウ、 高畠 清文、中野 敬介、長塚 仁
    • Organizer
      第67回日本病理学会秋期特別総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2026-01-16  

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