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Development of an in vivo chemical labeling method to label cancer-stromal interactions during metastasis

Research Project

Project/Area Number 22K19464
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionKansai Medical University

Principal Investigator

SAKAMOTO Takeharu  関西医科大学, 医学部, 教授 (70511418)

Project Period (FY) 2022-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsがん / 転移 / ケミカルラベリング
Outline of Research at the Start

がん転移はがん細胞と間質の細胞の相互作用により成立する。がん細胞-間質細胞の物理的な相互作用はがん細胞の血管内・外遊走に特に重要なステップであるが、間質中の細胞のごく一部の細胞が一過性にがん細胞と接着するため、生体でがん細胞と物理的相互作用をした間質細胞にどのような変化が起こっているかを包括的に解析する手法の開発が切望される。そこで、本研究ではケミカルラベリングの手法をin vivoの細胞標識に応用し、実験的肺転移モデルでのがん細胞の血管外遊走を解析の対象とし、血管内皮細胞の標識を目標とした、がん血管外遊走時の細胞間相互作用を標識するin vivo ケミカルラベリング法の開発を行う

Outline of Final Research Achievements

Mutational PCR for HRP and mgSrtA was performed to construct a transmembrane expression library, and mutants with high labeling efficiency were screened. The mutant was obtained. We transplanted EO771 cells with this mutant into the tail vein and administered Alexa488-LPETG peptide into the tail vein 4 hours after transplantation to see if it could label lung cells in contact with tumor cells such as vascular endothelial cells in vivo in a model of lung metastasis. Unfortunately, the in vivo labeling efficiency was not sufficient to distinguish it from the background.

Academic Significance and Societal Importance of the Research Achievements

今回の実験では残念ながらin vivoのラベリングに耐えうる変異体は得られなかった。本研究実施時に、SrtAとG5を用いたuLIPSTICの実験系によるin vivoラベリングの手法がNatureに報告されたが、本研究の手法を応用してG5の標識効率を上げるSrtA変異体の開発を行えばより、効率なラベリング手法の開発が期待される。

Report

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

    (42 results)

All 2025 2024 2023 2022 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 14 results) Presentation (27 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Mint3 as a Molecular Target Activated in the Early Stage of Hepatocarcinogenesis2025

    • Author(s)
      Nishitani Masaki、Okada Hikari、Nio Kouki、Hayashi Tomoyuki、Terashima Takeshi、Iida Noriho、Shimakami Tetsuro、Takatori Hajime、Honda Masao、Kaneko Shuichi、Sakamoto Takeharu、Yamashita Taro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 26 Issue: 4 Pages: 1430-1430

    • DOI

      10.3390/ijms26041430

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis2024

    • Author(s)
      Hashimoto Masahiro、Kojima Yasuhiro et. al.
    • Journal Title

      eBioMedicine

      Volume: 103 Pages: 105102-105102

    • DOI

      10.1016/j.ebiom.2024.105102

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集 がん遺伝子の発見は現代医療を進歩させたか Ⅰ.がん遺伝子研究の新しい展開 RAS遺伝子を中心としたがん治療戦略の確立2023

    • Author(s)
      田中 伯享、坂本 毅治
    • Journal Title

      生体の科学

      Volume: 74 Issue: 4 Pages: 289-294

    • DOI

      10.11477/mf.2425201695

    • ISSN
      0370-9531, 1883-5503
    • Year and Date
      2023-08-15
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of oxygen-sensing mechanism modulator, Mint3, in macrophage-related infl ammation and cancer2023

    • Author(s)
      坂本 毅治、田中 伯享、植松 崇之
    • Journal Title

      Cytometry Research

      Volume: 32 Issue: 2 Pages: 1-9

    • DOI

      10.18947/cytometryresearch.32.2_1

    • ISSN
      0916-6920, 2424-0664
    • Year and Date
      2023-04-17
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mint3-depletion-induced energy stress sensitizes triple-negative breast cancer to chemotherapy via HSF1 inactivation2023

    • Author(s)
      Tanaka Noritaka、Okada Hikari、Yamaguchi Kiyoshi、Seki Masahide、Matsubara Daisuke、Gotoh Noriko、Suzuki Yutaka、Furukawa Yoichi、Yamashita Taro、Inoue Jun-ichiro、Kaneko Shuichi、Sakamoto Takeharu
    • Journal Title

      Cell Death & Disease

      Volume: 14 Issue: 12 Pages: 815-815

    • DOI

      10.1038/s41419-023-06352-4

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MT1-MMP as a Key Regulator of Metastasis2023

    • Author(s)
      Tanaka Noritaka、Sakamoto Takeharu
    • Journal Title

      Cells

      Volume: 12 Issue: 17 Pages: 2187-2187

    • DOI

      10.3390/cells12172187

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent Progress on Genetically Modified Animal Models for Membrane Skeletal Proteins: The 4.1 and MPP Families2023

    • Author(s)
      Terada Nobuo、Saitoh Yurika、Saito Masaki、Yamada Tomoki、Kamijo Akio、Yoshizawa Takahiro、Sakamoto Takeharu
    • Journal Title

      Genes

      Volume: 14 Issue: 10 Pages: 1942-1942

    • DOI

      10.3390/genes14101942

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] L-2hydroxyglutaric acid rewires amino acid metabolism in colorectal cancer via the mTOR-ATF4 axis2023

    • Author(s)
      Tabata Sho、Kojima Yasushi、Sakamoto Takeharu、Igarashi Kaori、Umetsu Ko、Ishikawa Takamasa、Hirayama Akiyoshi、Kajino-Sakamoto Rie、Sakamoto Naoya、Yasumoto Ken-ichi、Okano Keiichi、Suzuki Yasuyuki、Yachida Shinichi、Aoki Masahiro、Soga Tomoyoshi
    • Journal Title

      Oncogene

      Volume: 42 Issue: 16 Pages: 1294-1307

    • DOI

      10.1038/s41388-023-02632-7

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatial and single-cell transcriptomics decipher the cellular environment containing HLA-G+ cancer cells and SPP1+ macrophages in colorectal cancer2023

    • Author(s)
      Ozato Y, Mimori K(28番目),他26名
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 1 Pages: 111929-111929

    • DOI

      10.1016/j.celrep.2022.111929

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia inducible factor‐1 activator munc‐18‐interacting protein 3 promotes tumour progression in urothelial carcinoma2023

    • Author(s)
      Ikeda Junichi、Ohe Chisato、Tanaka Noritaka、Yoshida Takashi、Saito Ryoichi、Atsumi Naho、Kobayashi Takashi、Kinoshita Hidefumi、Tsuta Koji、Sakamoto Takeharu
    • Journal Title

      Clinical and Translational Discovery

      Volume: 3 Issue: 1

    • DOI

      10.1002/ctd2.158

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mint3 as a Potential Target for Cooling Down HIF-1α-Mediated Inflammation and Cancer Aggressiveness2023

    • Author(s)
      Tanaka Noritaka、Sakamoto Takeharu
    • Journal Title

      Biomedicines

      Volume: 11 Issue: 2 Pages: 549-549

    • DOI

      10.3390/biomedicines11020549

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-homophilic interaction of CADM1 promotes organ infiltration of T-cell lymphoma by adhesion to vascular endothelium.2022

    • Author(s)
      Kasai Y, Gan SP, Funaki T, Ohashi-Kumagai Y, Tominaga M, Shiu S-J, Suzuki D, Matsubara D, Sakamoto T, Sakurai-Yageta M, Ito T, Murakami Y.
    • Journal Title

      Cancer Science

      Volume: in press Issue: 5 Pages: 1-2

    • DOI

      10.1111/cas.15307

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CHIP‐associated mutant ASXL1 in blood cells promotes solid tumor progression2022

    • Author(s)
      Liu Xiaoxiao、Sato Naru、Shimosato Yuko、Wang Teh‐Wei、Denda Tamami、Chang Yu‐Hsuan、Yabushita Tomohiro、Fujino Takeshi、Asada Shuhei、Tanaka Yosuke、Fukuyama Tomofusa、Enomoto Yutaka、Ota Yasunori、Sakamoto Takeharu、Kitamura Toshio、Goyama Susumu
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 4 Pages: 1182-1194

    • DOI

      10.1111/cas.15294

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of membrane palmitoylated protein 2 (MPP2) in the synaptic molecular complex at the mouse cerebellar glomerulus2022

    • Author(s)
      Tomoki Yamada, Yurika Saitoh, Kiyokazu Kametani, Akio Kamijo, Takeharu Sakamoto, Nobuo Terada
    • Journal Title

      Histochem Cell Biol

      Volume: 158 Issue: 5 Pages: 497-511

    • DOI

      10.1007/s00418-022-02137-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CRISPR/Cas9ライブラリーを用いた卵巣癌のアノイキス耐性遺伝子の探索2024

    • Author(s)
      森汐莉, Vu Duc Anh, 赤松香奈子, 安河内彦輝, 日笠幸一郎, 坂本毅治
    • Organizer
      第47回日本分子生物学会年会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 膀胱癌発がんモデルにおけるMint3が及ぼす影響2024

    • Author(s)
      生駒 龍興, 坂本 毅治, 森 汐莉
    • Organizer
      第83回日本癌学会学術総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 遺伝子改変マウスモデルを用いた細胞接着分子CADM1による小細胞肺がん悪性化機構の解析2024

    • Author(s)
      河原舞理恵, 舩城桐子, 伊東剛, 坂本毅治, 片山量平, 村上善則
    • Organizer
      第83回日本癌学会学術総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 消化管がん治療と診断における分子メカニズムとバイオマーカー2024

    • Author(s)
      橋本 雅弘, 小嶋 泰弘, 坂本 毅治, 増田 隆明, 井上 彬, 波多 豪, 植村 守, 江口 英利, 土岐 祐一郎, 鈴木 穣, 島村 徹平, 三森 功士
    • Organizer
      第83回日本癌学会学術総会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] KRAS阻害剤によるHIF-1Aの発現制御機構2024

    • Author(s)
      田中 伯享, 坂本 毅治
    • Organizer
      第83回日本癌学会学術総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Exploring genes involved in anoikis resistance in ovarian cancer using the CRISPR/Cas9 libraries2024

    • Author(s)
      Vu Duc Anh, 坂本 毅治, 森 汐莉
    • Organizer
      第83回日本癌学会学術総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] CRISPR/Cas9ライブラリーを用いた卵巣がんのアノイキス耐性に関わる遺伝子の網羅的探索2024

    • Author(s)
      Vu Duc Anh, 田中伯享, 坂本毅治
    • Organizer
      第33回日本がん転移学会学術集会・総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Mint3が膀胱癌の発がんから転移を促進させる2024

    • Author(s)
      生駒龍興, 森汐莉, 坂本毅治
    • Organizer
      第33回日本がん転移学会学術集会・総会
    • Related Report
      2024 Annual Research Report
  • [Presentation] KRAS阻害剤によるHIF-1alphaの翻訳制御2024

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第28回日本がん分子標的治療学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] KRAS阻害剤によるHIF-1Aの発現制御機構2023

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第46回分子生物学会年会
    • Related Report
      2023 Research-status Report
  • [Presentation] 細胞内酸素センシング調節機構を標的としたがん・炎症の制御2023

    • Author(s)
      坂本毅治
    • Organizer
      第64 回日本組織細胞化学会総会・学術集会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] KRAS阻害剤に対する耐性化とEMTに関する解析2023

    • Author(s)
      田中伯享、坂本毅治
    • Organizer
      第32回日本がん転移学会学術集会・総会
    • Related Report
      2023 Research-status Report
  • [Presentation] KRAS阻害剤によるHIF-1α発現制御メカニズム2023

    • Author(s)
      田中伯享、坂本毅治
    • Organizer
      第27回日本がん分子標的治療学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] The potential effect of KRAS inhibitors on tumor microenvironments2023

    • Author(s)
      Noritaka Tanaka, Takeharu Sakamoto
    • Organizer
      AACR-NCI-EORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS 2023
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] HIF-1 activator Mint3 promotes tumor progression in urothelial carcinoma2023

    • Author(s)
      Ikeda J, Ohe C, Tanaka N, Yoshida T, Saito R, Atsumi N, Kobayashi T, Kinoshita H, Tsuta K, Sakamoto T
    • Organizer
      第38回欧州泌尿器科学会議(EAU23 38th Annual EAU Congress)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 酸素センシング機構によるマクロファージ機能制御のがん、炎症性疾患における役割2022

    • Author(s)
      坂本毅治, 植松崇之
    • Organizer
      第32回日本サイトメトリー学会学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] KRAS阻害剤ががん微小環境に与える影響に関する検討2022

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第26回日本がん分子標的治療学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 化学療法誘導性肺転移の新規メカニズム2022

    • Author(s)
      坂本 毅治, 田中 伯享
    • Organizer
      第31回日本がん転移学会学術集会・総会
    • Related Report
      2022 Research-status Report
  • [Presentation] KRAS阻害剤に対する耐性と転移能に関する解析2022

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第31回日本がん転移学会学術集会・総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mint3は高分化型AFP陰性肝細胞癌に対する新規治療標的因子になり得る2022

    • Author(s)
      岡田光, 山下太郎, 坂本毅治, 金子周一
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mint3阻害はin vivoでトリプルネガティブ乳がんを化学療法感受性にする2022

    • Author(s)
      坂本毅治, 田中伯享, 山口貴世志, 松原大祐, 古川洋一
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] T細胞リンパ腫と血管内皮細胞間における細胞接着分子CADM1のトランス・ホモ結合は臓器浸潤を促進する2022

    • Author(s)
      笠井優, 坂本毅治, 伊東剛, 村上善則
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] KRAS阻害剤ががん微小環境のリプログラミングにおよぼす影響に関する解析2022

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mint3は膵癌でHIF-1を介してSKP2を制御する2022

    • Author(s)
      金森茜, 村上善則, 井上純一郎, 坂本毅治
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mint3は尿路上皮癌における予後不良因子である2022

    • Author(s)
      池田純一, 田中伯享, 齊藤亮一, 小林恭, 木下秀文, 坂本毅治
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] がんにおける低酸素応答関連因子に対するKRAS阻害剤の影響2022

    • Author(s)
      田中伯享, 坂本毅治
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] The collateral effects of KRAS inhibitors on tumor microenvironment2022

    • Author(s)
      Noritaka Tanaka, Takeharu Sakamoto
    • Organizer
      The 26th JFCR-ISCC
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] 関西医科大学附属生命医学研究所がん生物学部門HP

    • URL

      https://take-sakamoto-lab.jimdosite.com/

    • Related Report
      2024 Annual Research Report 2023 Research-status Report 2022 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2026-01-16  

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