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Anaysis of tumor and reprogramming based on chronic inflammation

Research Project

Project/Area Number 19H03452
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionOsaka University

Principal Investigator

Morii Eiichi  大阪大学, 大学院医学系研究科, 教授 (10283772)

Co-Investigator(Kenkyū-buntansha) 奥崎 大介  大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (00346131)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords慢性炎症 / 腫瘍 / 遺伝子発現制御 / epigenetic制御 / 免疫染色 / 肺癌 / 遺伝子発現 / クロマチン制御 / 腫瘍の多様性 / 炎症 / 多様性 / リモデリング / 病理
Outline of Research at the Start

通常、細胞は未分化な状態から分化した状態に移行する。しかし、慢性炎症では分化状態から未分化な状態に戻るリプログラミングが起こることがある。慢性炎症を背景とした腫瘍はde novo発生の腫瘍と比べ形態的な異型度は弱いにも関わらず悪性度が高い。リプログラミングを経た未分化細胞が腫瘍化した場合は、通常の未分化細胞と比較して「分化のメモリー」が内在化しており、通常の腫瘍よりも分化する傾向が強く、その結果、病理形態学的に捉えられない状況で腫瘍化が起こっているのかもしれない。慢性間質性肺炎由来肺腫瘍と通常の肺腫瘍におけるepigeneticパターンを比較することで、分化のメモリーの実態を明らかにする。

Outline of Final Research Achievements

Tumors induced by chronic inflammation are highly diverse. The diversity is generated by differences in gene expression patterns. In this study, we investigated the epigenetic regulatory mechanisms that generate tumor diversity using pathological specimens. We found that the expression patterns of EZH2, which causes methylation of the 27th lysine of histone H3, and H3K27me3, which trimethylates H3K27, are mutually exclusive. We further found that the ratio of the amount of SMARCA2 and SMARCA4, two factors with ATPase activity in the another epigenetic regulator SWI/SNF complex, correlated with tumor grade. Furthermore, we succeeded in generating organoids for each alveolar and bronchial organ and established a model system to study the effects of chronic inflammation on gene expression.

Academic Significance and Societal Importance of the Research Achievements

慢性炎症を背景に発生する腫瘍は予後不良で形態学的にも多様性に富んでいる。多様性とは発現する遺伝子パターンの違いに帰着でき、慢性炎症と遺伝子発現パターンを制御する因子との間に何らかの関係があることが予想される。それを解析するためには、まず腫瘍の多様性と遺伝子発現パターン制御因子を調べる必要がある。遺伝子発現パターンの制御はepigeneticなレベルで起こっている。そこで、epigeneticな状況を制御する様々な因子と腫瘍形態との関連を病理検体を用いて解析した。その結果、多様性を生み出す因子と腫瘍形態とに相関性があることがわかり、この制御により腫瘍の予後を改善することが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (18 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 18 results,  Open Access: 12 results) Presentation (9 results) (of which Invited: 9 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Ovarian high‐grade serous carcinoma cells with low SMARCA4 expression and high SMARCA2 expression contribute to platinum resistance2023

    • Author(s)
      Kido Kansuke、Nojima Satoshi、Motooka Daisuke、Nomura Yusuke、Kohara Masaharu、Sato Kazuaki、Ohshima Kenji、Tahara Shinichiro、Kurashige Masako、Umeda Daisuke、Takashima Tsuyoshi、Kiyokawa Hiroki、Ukon Koto、Matsui Takahiro、Okuzaki Daisuke、Morii Eiichi
    • Journal Title

      The Journal of Pathology

      Volume: 260 Issue: 1 Pages: 56-70

    • DOI

      10.1002/path.6064

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor cell plasticity in endometrioid carcinoma is regulated by neuronal membrane glycoprotein M6?b2022

    • Author(s)
      Kusumoto Shinya、Ikeda Jun-Ichiro、Kurashige Masako、Maeno-Fujinami Etsuko、Tahara Shinichiro、Matsui Takahiro、Nojima Satoshi、Okuzaki Daisuke、Morii Eiichi
    • Journal Title

      Oncology Letters

      Volume: 25 Issue: 2 Pages: 45-45

    • DOI

      10.3892/ol.2022.13631

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutually exclusive expression of EZH2 and H3K27me3 in non-small cell lung carcinoma2022

    • Author(s)
      Onishi Takafumi、Takashima Tsuyoshi、Kurashige Masako、Ohshima Kenji、Morii Eiichi
    • Journal Title

      Pathology - Research and Practice

      Volume: 238 Pages: 154071-154071

    • DOI

      10.1016/j.prp.2022.154071

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Three-Dimensional Imaging System Based on Polysaccharide Staining for Accurate Histopathological Diagnosis of Inflammatory Bowel Diseases2022

    • Author(s)
      Nojima Satoshi、Ishida Shoichi、Terayama Kei、Matsumoto Katsuhiko、Matsui Takahiro、Tahara Shinichiro、Ohshima Kenji、Kiyokawa Hiroki、Kido Kansuke、Ukon Koto、Yoshida Shota Y.、Mitani Tomoki T.、Doki Yuichiro、Mizushima Tsunekazu、Okuno Yasushi、Susaki Etsuo A.、Ueda Hiroki R.、Morii Eiichi
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 14 Issue: 4 Pages: 905-924

    • DOI

      10.1016/j.jcmgh.2022.07.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep Learning Analysis of Histologic Images from Intestinal Specimen Reveals Adipocyte Shrinkage and Mast Cell Infiltration to Predict Postoperative Crohn Disease2022

    • Author(s)
      Kiyokawa H, Abe M, Matsui T, Kurashige M, Ohshima K, Tahara S, Nojima S, Ogino T, Sekido Y, Mizushima T, Morii E.
    • Journal Title

      Am J Pathol .

      Volume: 22 Issue: 6 Pages: 106-7

    • DOI

      10.1016/j.ajpath.2022.03.006

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strong expression of PD-L1 in invasive front of MELF pattern in endometrioid carcinoma2022

    • Author(s)
      Tahara S, Kohara M, Sato K, Morii E.
    • Journal Title

      Pathol Res Pract .

      Volume: 229 Pages: 153699-153699

    • DOI

      10.1016/j.prp.2021.153699

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondria govern histone acetylation in colorectal cancer2021

    • Author(s)
      Ohshima Kenji、Oi Ryo、Nojima Satoshi、Morii Eiichi
    • Journal Title

      The Journal of Pathology

      Volume: 256 Issue: 2 Pages: 164-173

    • DOI

      10.1002/path.5818

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial matrix protein C14orf159 attenuates colorectal cancer metastasis by suppressing Wnt/β-catenin signalling2021

    • Author(s)
      Ohshima Kenji、Oi Ryo、Okuzaki Daisuke、Motooka Daisuke、Shinohara Masakazu、Nojima Satoshi、Morii Eiichi
    • Journal Title

      British Journal of Cancer

      Volume: 125 Issue: 12 Pages: 1699-1711

    • DOI

      10.1038/s41416-021-01582-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma2021

    • Author(s)
      Tahara S, Nojima S, Ohshima K, Hori Y, Sato K, Kurashige M, Matsui T, Okuzaki D, Morii E.
    • Journal Title

      Cancer Med .

      Volume: 10 Issue: 23 Pages: 8630-8640

    • DOI

      10.1002/cam4.4359

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An immature inhibin‐α‐expressing subpopulation of ovarian clear cell carcinoma cells is related to an unfavorable prognosis2021

    • Author(s)
      Kusumoto Shinya、Kurashige Masako、Ohshima Kenji、Tahara Shinichiro、Matsui Takahiro、Nojima Satoshi、Hattori Satoshi、Morii Eiichi
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 5 Pages: 1485-1500

    • DOI

      10.1002/cam4.3801

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic suppression of SLFN11 in germinal center B-cells during B-cell development2021

    • Author(s)
      Moribe F, Nishikori M, Takashima T, Taniyama D, Onishi N, Arima H, Sasanuma H, Akagawa R, Elloumi F, Takeda S, Pommier Y, Morii E, Takaori-Kondo A, Murai J.
    • Journal Title

      PLoS One.

      Volume: 16 Issue: 1 Pages: 0237554-0237554

    • DOI

      10.1371/journal.pone.0237554

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis.2021

    • Author(s)
      Ohshima K, Morii E.
    • Journal Title

      Metabolites.

      Volume: 11 Issue: 1 Pages: 28-28

    • DOI

      10.3390/metabo11010028

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The expression of trefoil factor 3 is related to histologic subtypes and invasiveness in lung adenocarcinoma.2021

    • Author(s)
      Luo W, Tahara S, Kawasaki K, Kobayashi A, Nojima S, Morii E.
    • Journal Title

      Oncol Lett.

      Volume: 63 Issue: 1 Pages: 63-63

    • DOI

      10.3892/ol.2020.12325

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] HTR3A is correlated with unfavorable histology and promotes proliferation through ERK phosphorylation in lung adenocarcinoma2020

    • Author(s)
      Tone Mitsuyo、Tahara Shinichiro、Nojima Satoshi、Motooka Daisuke、Okuzaki Daisuke、Morii Eiichi
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 10 Pages: 3953-3961

    • DOI

      10.1111/cas.14592

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway2020

    • Author(s)
      Hori Yumiko、Hirose Katsutoshi、Aramaki-Hattori Noriko、Suzuki Sachi、Nakayama Robert、Inoue Masanori、Matsui Takahiro、Kohara Masaharu、Toyosawa Satoru、Morii Eiichi
    • Journal Title

      Diagnostic Pathology

      Volume: 15 Issue: 1 Pages: 98-98

    • DOI

      10.1186/s13000-020-01004-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumour Grade Significantly Correlates With Total Dysfunction of Tumour Tissue-Infiltrating Lymphocytes in Renal Cell Carcinoma2020

    • Author(s)
      Kawashima A, Kanazawa T, Kidani Y, Yoshida T, Hirata M, Nishida K, Nojima S, Yamamoto Y, Kato T, Hatano K, Ujike T, Nagahara A, Fujita K, Morimoto-Okazawa A, Iwahori K, Uemura M, Imamura R, Ohkura N, Morii E, Sakaguchi S, Wada H, Nonomura N.
    • Journal Title

      Sci Rep .

      Volume: 10 Issue: 1 Pages: 6220-6220

    • DOI

      10.1038/s41598-020-63060-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target2020

    • Author(s)
      Kimura Kenji、Matsumoto Shinji、Harada Takeshi、Morii Eiichi、Nagatomo Izumi、Shintani Yasushi、Kikuchi Akira
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 3 Pages: 951-961

    • DOI

      10.1111/cas.14303

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SDPR Regulates ALDH1 via ILK Signaling in Endometrioid Carcinoma Cells.2019

    • Author(s)
      Tahara S, Nojima S, Ohshima K, Hori Y, Kurashige M, Wada N, Motoyama Y, Okuzaki D, Ikeda JI, Morii E.
    • Journal Title

      Cancer Sci.

      Volume: in press Issue: 5 Pages: 1804-1813

    • DOI

      10.1111/cas.14007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 多様性という視点からみた腫瘍動態2023

    • Author(s)
      森井英一
    • Organizer
      第47回大阪府臨床細胞学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腫瘍の多様性2023

    • Author(s)
      森井英一
    • Organizer
      第31回愛媛県臨床細胞学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腫瘍の多様性を担う因子の解析2022

    • Author(s)
      森井英一
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 幹細胞の観点から考える子宮内膜癌のバイオロジー2022

    • Author(s)
      森井英一
    • Organizer
      第61回日本臨床細胞学会秋期大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 創薬研究における薬理―病理連携の必要性2022

    • Author(s)
      森井英一
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腫瘍の多様性を担う因子の解析―病理検体から学ぶこと2022

    • Author(s)
      森井英一
    • Organizer
      第111回日本病理学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 病理標本から伺える疾患メカニズム2021

    • Author(s)
      森井英一
    • Organizer
      第17回日本病理学会カンファレンス
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Heterogeneity of Tumor Cells from the Viewpoint of Pathological Specimen2020

    • Author(s)
      森井英一
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 病理診断におけるAIと専門医のあり方2019

    • Author(s)
      森井英一
    • Organizer
      日本学術会議公開シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] 実践細胞診テキスト(改訂版)2022

    • Author(s)
      南雲サチ子、森井英一
    • Total Pages
      409
    • Publisher
      大阪大学出版会
    • ISBN
      9784872597554
    • Related Report
      2021 Annual Research Report
  • [Remarks] 卵巣がんのプラチナ抵抗性に関与する特殊な細胞群を同定

    • URL

      https://resou.osaka-u.ac.jp/ja/research/2023/20230301_2

    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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