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2022 Fiscal Year Annual Research Report

Exploration of the origin of intratumoral heterogeneity in squamous cell carcinoma by single-cell analysis

Research Project

Project/Area Number 20K08698
Research InstitutionNippon Medical School

Principal Investigator

佐伯 秀久  日本医科大学, 大学院医学研究科, 大学院教授 (80235093)

Co-Investigator(Kenkyū-buntansha) 長田 真一  日本医科大学, 医学部, 准教授 (00244484)
平谷 伊智朗  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (40583753)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywords腫瘍内不均一性 / 有棘細胞がん / 微小環境 / RNA-Seq / シグナル伝達
Outline of Annual Research Achievements

がんは従来、1つの細胞に由来する、クローナルな細胞集団と考えられてきたが、ゲノム異常の蓄積、微小環境の影響により、一つの腫瘍の中にゲノムの異なる、多数のサブクローンが存在することがわかり、この現象は腫瘍内不均一性と呼ばれる。腫瘍内不均一性は、がんが治療抵抗性を獲得し、再発・転移する分子基盤であると考えられるが、微小環境の影響を解析する方法は確立していない。
我々はマウスにできた有棘細胞がん(SCC)から樹立した細胞株を、遺伝的バックグランドが同じマウスに注射することにより (allograft モデル)、SCCを再現する系を独自に確立した。本研究の目的は、この系を用いて、2次元の培養SCC細胞から3次元のSCC組織ができる時に、どのような遺伝子の発現の違いがみられるのかをRNA-Seqの手法で比較し、がん微小環境によりSCC内に不均一性が生じるメカニズムを明らかにすることである。
本研究は当初、上述の解析を、シングルセルレベルで行うことを目標としていたが、がん組織を酵素などでシングルセルにした時点で3次元構築に関わる遺伝子の発現がダウンレギュレーションする可能性があること、SCC組織は表皮細胞間の接着が強く、シングルセルにすることが困難であったことなどから、まず、培養SCC細胞(2次元)とそれをマウスに皮下注射してできたからSCC組織(3次元)の遺伝子発現を、集団(バルク)として解析することにした。RNA-Seqでは、培養SCC細胞群(3検体)と3次元SCC組織群(3検体)で、低発現量の遺伝子を除外した、15,877遺伝子の発現量を比較した。その結果、発現量が増加した遺伝子が4,328、発現量が低下した遺伝子が4,312見つかった。発現が増加した遺伝子についてパスウェイ解析したところ、炎症性サイトカインの発現が非常に上昇していることが判明した。

  • Research Products

    (17 results)

All 2023 2022

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 13 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Barrier Factors of Adherence to Dupilumab Self-Injection for Severe Allergic Disease: A Non-Interventional Open-Label Study2023

    • Author(s)
      Hosoya Kei、Komachi Taro、Masaki Katsunori、Suzaki Isao、Saeki Hidehisa、Kanda Naoko、
    • Journal Title

      Patient Preference and Adherence

      Volume: Volume 17 Pages: 861~872

    • DOI

      10.2147/PPA.S389865

    • Peer Reviewed / Open Access
  • [Journal Article] Recurrence or de novo? Intradermal Basal Cell Carcinoma of the Scrotum: A Report of Two Cases2023

    • Author(s)
      Yamazaki Kaori、Maejima Maho、Saeki Hidehisa、Osada Shin-Ichi
    • Journal Title

      Dermatopathology

      Volume: 10 Pages: 128~135

    • DOI

      10.3390/dermatopathology10020019

    • Peer Reviewed / Open Access
  • [Journal Article] Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial2022

    • Author(s)
      Saeki Hidehisa、Ito Kensuke、Yokota Daisuke、Tsubouchi Hidetsugu
    • Journal Title

      Journal of the American Academy of Dermatology

      Volume: 86 Pages: 607~614

    • DOI

      10.1016/j.jaad.2021.10.027

    • Peer Reviewed / Open Access
  • [Journal Article] Real‐world blood examination screening data before initiation of biologics for psoriasis patients2022

    • Author(s)
      Ozaki Saeko、Ichiyama Susumu、Ito Michiko、Hoashi Toshihiko、Kanda Naoko、Saeki Hidehisa
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Pages: 534~538

    • DOI

      10.1111/1346-8138.16333

    • Peer Reviewed
  • [Journal Article] Effectiveness of brodalumab in achieving treatment satisfaction for patients with plaque psoriasis: The ProLOGUE study2022

    • Author(s)
      Imafuku Shinichi、Ohata Chika、Okubo Yukari、Tobita Rie、Saeki Hidehisa、Mabuchi Tomotaka、Hashimoto Yuki、Murotani Kenta、Kitabayashi Hiroki、Kanai Yasumasa
    • Journal Title

      Journal of Dermatological Science

      Volume: 105 Pages: 176~184

    • DOI

      10.1016/j.jdermsci.2022.02.007

    • Peer Reviewed / Open Access
  • [Journal Article] Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study2022

    • Author(s)
      Saeki Hidehisa、Imamura Tomomi、Yokota Daisuke、Tsubouchi Hidetsugu
    • Journal Title

      Dermatology and Therapy

      Volume: 12 Pages: 1589~1601

    • DOI

      10.1007/s13555-022-00751-9

    • Peer Reviewed / Open Access
  • [Journal Article] A phase 3 randomized, multicenter, double-blind study to evaluate the safety of upadacitinib in combination with topical corticosteroids in adolescent and adult patients with moderate-to-severe atopic dermatitis in Japan (Rising Up): An interim 24-week analysis2022

    • Author(s)
      Katoh Norito、Ohya Yukihiro、Murota Hiroyuki、Ikeda Masanori、Hu Xiaofei、Ikeda Kimitoshi、Liu John、Sasaki Takuya、Chu Alvina D.、Teixeira Henrique D.、Saeki Hidehisa
    • Journal Title

      JAAD International

      Volume: 6 Pages: 27~36

    • DOI

      10.1016/j.jdin.2021.11.001

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An economic evaluation of risankizumab versus other biologic treatments of moderate to severe plaque psoriasis in Japan2022

    • Author(s)
      Saeki Hidehisa、Ishii Kanako、Joshi Avani、Bensimon Arielle G.、Yang Hongbo、Kawaguchi Isao
    • Journal Title

      Journal of Dermatological Treatment

      Volume: 33 Pages: 229~239

    • DOI

      10.1080/09546634.2020.1744505

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of standard treatments for managing adult Japanese patients with inadequately controlled moderate‐to‐severe atopic dermatitis: Two‐year data from the <scp>ADDRESS‐J</scp> disease registry2022

    • Author(s)
      Katoh Norito、Saeki Hidehisa、Kataoka Yoko、Etoh Takafumi、Teramukai Satoshi、Takagi Hiroki、Fujita Hiroyuki、Ardeleanu Marius、Rizova Elena、Arima Kazuhiko、the ADDRESS‐J Investigators
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Pages: 903~911

    • DOI

      10.1111/1346-8138.16485

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular Mechanisms and Targeted Therapies of Advanced Basal Cell Carcinoma2022

    • Author(s)
      Hoashi Toshihiko、Kanda Naoko、Saeki Hidehisa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 11968~11968

    • DOI

      10.3390/ijms231911968

    • Peer Reviewed / Open Access
  • [Journal Article] Work productivity in real‐life employed patients with plaque psoriasis: Results from the ProLOGUE study2022

    • Author(s)
      Saeki Hidehisa、Kanai Yasumasa、Murotani Kenta、Ito Kei、Miyagi Takuya、Takahashi Hidetoshi、Tada Yayoi、Higashiyama Mari、Hashimoto Yuki、Kitabayashi Hiroki、Imafuku Shinichi
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Pages: 970~978

    • DOI

      10.1111/1346-8138.16517

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proactive versus Rank-Down Topical Corticosteroid Therapy for Maintenance of Remission in Pediatric Atopic Dermatitis: A Randomized, Open-Label, Active-Controlled, Parallel-Group Study (Anticipate Study)2022

    • Author(s)
      Kamiya Koji、Saeki Hidehisa、Tokura Yoshiki、Yoshihara Shigemi、Sugai Junichi、Ohtsuki Mamitaro
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Pages: 6477~6477

    • DOI

      10.3390/jcm11216477

    • Peer Reviewed / Open Access
  • [Journal Article] Long-term 2-year safety and efficacy of tralokinumab in adults with moderate-to-severe atopic dermatitis: Interim analysis of the ECZTEND open-label extension trial2022

    • Author(s)
      Blauvelt Andrew、Langley Richard G.、Lacour Jean-Philippe、Toth Darryl、Laquer Vivian、Beissert Stefan、Wollenberg Andreas、Herranz Pedro、Pink Andrew E.、Peris Ketty、Fangel Stine、Gjerum Le、Corriveau Joshua、Saeki Hidehisa、Warren Richard B.、Simpson Eric、Reich Kristian
    • Journal Title

      Journal of the American Academy of Dermatology

      Volume: 87 Pages: 815~824

    • DOI

      10.1016/j.jaad.2022.07.019

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pooled Safety Analysis of Baricitinib in Adult Participants with Atopic Dermatitis in the Japanese Subpopulation from Six Randomized Clinical Trials2022

    • Author(s)
      Katoh Norito、Takita Yasushi、Isaka Yoshitaka、Nishikawa Atsushi、Torisu-Itakura Hitoe、Saeki Hidehisa
    • Journal Title

      Dermatology and Therapy

      Volume: 12 Pages: 2765~2779

    • DOI

      10.1007/s13555-022-00828-5

    • Peer Reviewed / Open Access
  • [Journal Article] Collagen XVII deficiency alters epidermal patterning2022

    • Author(s)
      Wang Yunan、Kitahata Hiroyuki、Kosumi Hideyuki、Watanabe Mika、Fujimura Yu、Takashima Shota、Osada Shin-Ichi、Hirose Tomonori、Nishie Wataru、Nagayama Masaharu、Shimizu Hiroshi、Natsuga Ken
    • Journal Title

      Laboratory Investigation

      Volume: 102 Pages: 581~588

    • DOI

      10.1038/s41374-022-00738-2

    • Peer Reviewed
  • [Journal Article] Large-Scale Chromatin Rearrangements in Cancer2022

    • Author(s)
      Yamaguchi Kosuke、Chen Xiaoying、Oji Asami、Hiratani Ichiro、Defossez Pierre-Antoine
    • Journal Title

      Cancers

      Volume: 14 Pages: 2384~2384

    • DOI

      10.3390/cancers14102384

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Real-world safety and one-year effectiveness of dupilumab in Japanese patients with atopic dermatitis2022

    • Author(s)
      Fujita H, Suzuki K, Arima K, Saeki H
    • Organizer
      Annual Meeting of the American Academy of Dermatology
    • Int'l Joint Research

URL: 

Published: 2023-12-25  

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