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Analysis of the characteristics of Side Population cells derived from oral squamous cell carcinoma as cancer stem cells

Research Project

Project/Area Number 18K09744
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHiroshima University

Principal Investigator

Toratani Shigeaki  広島大学, 医系科学研究科(歯), 准教授 (90172220)

Co-Investigator(Kenkyū-buntansha) 岡本 哲治  広島大学, 医系科学研究科(歯), 教授 (00169153)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords癌幹細胞 / 口腔扁平上皮癌 / Side population / Hif-1α / CD133 / ガン幹細胞 / 低酸素環境 / HIF-1α / side poulation / side population / 低酸素状態
Outline of Final Research Achievements

The aim of this study was to establish a cancer stem cell model. Taking advantage of the fact that cancer stem cells highly express a group of fluorescent dye efflux molecules, we isolated the side population (SP) cells with low fluorescence intensity from squamous cell carcinoma cells by FACS and analyzed their biological characteristics.
SP cells, like cancer stem cells, showed low proliferative potential, high sphere-forming ability and resistance to anticancer drugs. In addition, a small number of cells formed tumors at a high rate in nude mice. Culture of parental cells under hypoxia or gene transfer of the hypoxia response factor HIF-1α increased the proportion of SP cells. In contrast, suppression of CD133, a cancer stem cell marker, by siRNA decreased the proportion of SP cells. These results suggest that SP cells may function as cancer stem cells in a hypoxic environment.

Academic Significance and Societal Importance of the Research Achievements

口腔癌治療の基本は,外科的切除である。しかし進展癌や再発・転移癌に対しては放射線療法や化学療法が適応されるが,根治を得ることは困難なことが多い。その原因として,抗癌剤や放射線に耐性を示す癌幹細胞の存在が示唆されている。そこで癌幹細胞を分離・回収し,その細胞生物学的特性を解明することは,効果的な治療法を開発するためにも重要である。
癌幹細胞の分離する方法として細胞表面の癌幹細胞マーカーを目印にする方法や細胞機能の相違を利用する方法がある。本研究では,癌幹細胞が高発現している細胞外への薬剤の排出を担うABCトランスポーター分子の機能を利用し回収した細胞群が,癌幹細胞モデルになるかを検討した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2021 2020 2019 2018 2017

All Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 18 results,  Open Access: 11 results) Presentation (8 results)

  • [Journal Article] Age-related changes in oral tactile and thermal sensation throughout adulthood2021

    • Author(s)
      Nishimura Rumi、Yoshida Mitsuyoshi、Shigeishi Hideo、Fukada-Sambuichi Eri、Yamashita-Urabe Kaoru、Takechi Masaaki、Toratani Shigeaki、Tsuga Kazuhiro、Sugiyama Masaru
    • Journal Title

      Odontology

      Volume: - Issue: 3 Pages: 710-718

    • DOI

      10.1007/s10266-021-00594-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced KRT13 gene expression bestows radiation resistance in squamous cell carcinoma cells.2021

    • Author(s)
      Nguyen TQ, Hamada A, Yamada K, Higaki M, Shintani T, Yoshioka Y, Toratani S, Okamoto T
    • Journal Title

      In Vitro Cellular & Developmental Biology-Animal.

      Volume: 57(3) Issue: 3 Pages: 300-314

    • DOI

      10.1007/s11626-020-00542-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A case of maxillary ameloblastic carcinoma with atypical histology2021

    • Author(s)
      Hamana Tomoaki、Hayashido Yasutaka、Mishima Takefumi、Hirota Suguru、Hamada Atsuko、Ando Toshinori、Miyauchi Mutsumi、Toratani Shigeaki
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: - Issue: 5 Pages: 536-545

    • DOI

      10.1016/j.ajoms.2021.03.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bosutinib-induced osteonecrosis of the jaw in a patient with chronic myeloid leukemia: a case report2021

    • Author(s)
      Myoken Yoshinari、Fujita Yoshinori、Imanaka Ryota、Toratani Shigeaki
    • Journal Title

      Oral and Maxillofacial Surgery

      Volume: - Issue: 3 Pages: 421-425

    • DOI

      10.1007/s10006-020-00931-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Teriparatide Treatment for Medication-Related Osteonecrosis of the Jaw: Is This an Effective Option?2021

    • Author(s)
      Myoken Yoshinari、Fujita Yoshinori、Toratani Shigeaki
    • Journal Title

      Journal of Clinical Oncology

      Volume: 39 Issue: 2 Pages: 172-173

    • DOI

      10.1200/jco.20.02379

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MICA A5.1 homozygous genotype is associated with a risk for early-onset oral cancer2021

    • Author(s)
      Tani R, Nanako Ito R, Matsui K, Yamasaki S, Hamada A, Tokumaru K, Toratani S, Okamoto T.
    • Journal Title

      Oral Oncology

      Volume: 116, May Pages: 105256-105256

    • DOI

      10.1016/j.oraloncology.2021.105256

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel PTCH1 mutations in Japanese familial nevoid basal cell carcinoma syndrome2020

    • Author(s)
      Nakase Y., Hamada A., Kitamura N., Hata T., Toratani S., Yamamoto T., Okamoto T.
    • Journal Title

      Hum Genome Var

      Volume: 7(1) Issue: 1 Pages: 38-38

    • DOI

      10.1038/s41439-020-00126-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comment on "The effect of using a mobile application (‘WhiteTeeth’) on improving oral hygiene: A randomized controlled trial" by Scheerman et al2020

    • Author(s)
      Myoken Yoshiko、Myoken Yoshinari、Toratani Shigeaki
    • Journal Title

      International Journal of Dental Hygiene

      Volume: 18 Issue: 4 Pages: 439-440

    • DOI

      10.1111/idh.12464

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Kikuchi-Fujimoto disease after a cervical lymph node metastasis of mucoepidermoid carcinoma2020

    • Author(s)
      Higaki M, Kanda T, Ando T, Tani R, Toratani S
    • Journal Title

      Oral Maxillofac Surg.

      Volume: 24 Issue: 1 Pages: 133-137

    • DOI

      10.1007/s10006-020-00900-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteonecrosis of the jaw in a metastatic lung cancer patient with bone metastases undergoing pembrolizumab + denosumab combination therapy: Case report and literature review2020

    • Author(s)
      Myoken Yoshinari、Fujita Yoshinori、Kawamoto Kazuma、Toratani Shigeaki
    • Journal Title

      Oral Oncology

      Volume: 111 Pages: 104874-104874

    • DOI

      10.1016/j.oraloncology.2020.104874

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral squamous cell carcinoma of the tongue dorsum with multiple cancer-associated mutations in the TP53 gene2020

    • Author(s)
      Yamasaki Sachiko、Tani Ryouji、Sakurai Shigeru、Toratani Shigeaki、Okamoto Tetsuji
    • Journal Title

      Oral Oncology

      Volume: 109 Pages: 104774-104774

    • DOI

      10.1016/j.oraloncology.2020.104774

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of integration-free human-induced pluripotent stem cells under serum- and feeder-free conditions.2020

    • Author(s)
      Atsuko Hamada, Eri Akagi, Sachiko Yamasaki, Hirotaka Nakatao, Fumitaka Obayashi, Manami Ohtaka, Ken Nishimura, Mahito Nakanishi, Shigeaki Toratani & Tetsuji Okamoto
    • Journal Title

      In Vitro Cell Dev Biol Anim.

      Volume: 56(1) Issue: 1 Pages: 85-95

    • DOI

      10.1007/s11626-019-00412-w

    • NAID

      120007132728

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adolescent and Young Adult(AYA)世代における口腔がんの臨床的検討.2019

    • Author(s)
      吉岡幸男,坂上泰士,松井健作,津島康司,大林史誠,濱田充子,山崎佐知子,浜名智昭,角 健作,神田 拓,小泉浩一,谷 亮治,林堂安貴,笹原妃佐子,伊藤 翼,佐渡友浩, 石田康隆,岡本康正,小林雅史,坂本哲彦,明見能成,虎谷茂昭,岡本哲治.
    • Journal Title

      口科誌

      Volume: 68 Pages: 20-27

    • NAID

      130007626839

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 90歳以上の超高齢口腔がん患者の臨床的検討2019

    • Author(s)
      坂上泰士,吉岡幸男,松井健作,津島康司,大林史誠,濱田充子,山崎佐知子,浜名智昭,角 健作,神田 拓,小泉浩一,谷 亮治,林堂安貴,笹原妃佐子,伊藤 翼,佐渡友浩,石田康隆,岡本康正,小林雅史,坂本哲彦,明見能成,虎谷茂昭,岡本哲治.
    • Journal Title

      口科誌

      Volume: 68 Pages: 12-19

    • NAID

      130007626841

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 骨吸収抑制薬関連顎骨壊死(ARONJ: anti-resorptive agent-related osteonecrosis of the jaw)患者に生じた深頸部感染症の3例2019

    • Author(s)
      山崎佐知子,虎谷茂昭,内迫香織,田口有紀,吉岡幸男,岡本哲治
    • Journal Title

      口科誌

      Volume: 68 Pages: 226-231

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathological factors involved in local failure in squamous cell carcinoma of the oral cavity: retrospective study and proposal of a new clinical classification.2019

    • Author(s)
      Toratani S, Ogawa I, Sasahara H, Yoshioka Y, Kanda T, Tani R, Okamoto T.
    • Journal Title

      Int J Oral Maxillofac Surg.

      Volume: 48 Issue: 2 Pages: 143-151

    • DOI

      10.1016/j.ijom.2018.07.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suture granulomas developing after the treatment of oral squamous cell carcinoma2018

    • Author(s)
      Yoshioka Y, Nakatao H, Hamana T, Hamada A, Kanda T, Koizumia K, Toratani S, Okamoto T
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 50 Pages: 68-71

    • DOI

      10.1016/j.ijscr.2018.07.021

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report2017

    • Author(s)
      Nagasaki Atsuhiro、Ogawa Ikuko、Sato Yukiko、Takeuchi Kengo、Kitagawa Masae、Ando Toshinori、Sakamoto Shinnichi、Shrestha Madhu、Uchisako Kaori、Koizumi Koichi、Toratani Shigeaki、Konishi Masaru、Takata Takashi
    • Journal Title

      Pathology International

      Volume: 68 Issue: 1 Pages: 31-35

    • DOI

      10.1111/pin.12609

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔扁平上皮癌におけるhuman papilloma virus(HPV)16の関与.2019

    • Author(s)
      林 靖也, 虎谷茂昭,中峠洋隆,松井健作,福谷多恵子,濱田充子,吉岡幸男,谷亮治,岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 無血清培養系を用いた扁平上皮癌細胞の放射線耐性獲得機構の細胞内分泌学的 機能解析2019

    • Author(s)
      内迫香織,濱田充子,三島健史,松井健作,谷亮治,虎谷茂昭,岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 無血清培養系での口腔癌由来細胞株の樹立.2019

    • Author(s)
      濱田充子,佐藤成紀,内迫香織,中瀬洋司,大林史誠,中峠洋隆,山崎佐知子,谷 亮治,虎谷茂昭,岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔原発神経内分泌癌由来細胞株の樹立 初代培養腫瘍細胞の増殖様態から診断されるに至った口腔原発神経内分泌癌2019

    • Author(s)
      佐藤成紀,濱田充子,櫻井 繁,浜名智昭,虎谷茂昭,岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 基底細胞母斑症候群(NBCCS)の変異解析及びインテグレーションフリー・フィー ダーフリー・無血清培養系でのNBCCS 特異的iPSCの樹立2019

    • Author(s)
      中瀬洋司,濱田充子,中峠洋隆,大林 史誠,山崎佐知子,畑 毅,北村直也,山本哲也,虎谷茂昭,岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 9.Lymphokine-activated killer細胞の細胞障害活性の誘導に及ぼすコレステロール合成阻害剤の影響.2019

    • Author(s)
      三島健史, 谷 亮治, 松井健作, 内迫香織, 濱田充子, 虎谷茂昭, 岡本哲治.
    • Organizer
      第73回NPO法人日本口腔科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 10.次世代シーケンサーを用いた口腔癌患者の口腔内細菌叢の多様性解析.2019

    • Author(s)
      松井健作,谷亮治,濱田充子,虎谷茂昭,大友剛,徳丸浩一郎,岡本哲治.
    • Organizer
      第18回中国四国口腔癌研究会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔扁平上皮癌の局所再発に関する臨床・病理学的因子の後ろ向き検討 -新しい臨床分類の提案 -2018

    • Author(s)
      虎谷茂昭、小川郁子、笹原妃佐子、浜名智昭、神田 拓、小泉浩一、吉岡幸男、谷 亮治、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会中国・四国地方部
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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