Studies on biological properties of cancer stem cells in malignant mesothelioma

• Project/Area Number: 15K08370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hyogo College of Medicine
• Principal Investigator: Sato Ayuko 兵庫医科大学, 医学部, 講師 (20419823)
• Co-Investigator(Kenkyū-buntansha): 辻村 亨 兵庫医科大学, 医学部, 教授 (20227408) ; 篠原 義康 兵庫医科大学, 医学部, 助教 (60723509)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 悪性中皮腫 / がん幹細胞

Outline of Final Research Achievements

It is thought that cancer stem cells in malignant mesothelioma, mesothelioma stem cells, are involved in the resistance to treatment of malignant mesothelioma. When reprogramming factors for induced pluripotent stem cells were introduced into mesothelioma cell lines, colony forming cells appeared. The colony forming cells showed increase of spheroid formation, reduction of proliferation, and increase of resistance to an anticancer drug. In addition, in the colony forming cells, a cell adhesion molecule, which was found as a candidate for mesothelioma stem cell related factor by analyses of tumor specimens from recurrent malignant pleural mesothelioma, was more strongly expressed. Since these cells introduced with reprogramming factors showed characteristics as cancer stem cells, they may be useful to develop new diagnosis and therapy targeting mesothelioma stem cells.

Research Products

• [Journal Article] A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma. (2018)
  • Author(s): Kinoshita Yoshiaki、Hida Tomoyuki、Hamasaki Makoto、Matsumoto Shinji、Sato Ayuko、Tsujimura Tohru、Kawahara Kunimitsu、Hiroshima Kenzo、Oda Yoshinao、Nabeshima Kazuki
  • Journal Title: Cancer Cytopathol Volume: 126 Pages: 54-63
  • DOI: 10.1002/cncy.21928
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry. (2017)
  • Author(s): Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Iwasaki A, Okamoto T, Oda Y, Honda H, Nabeshima K.
  • Journal Title: Lung Cancer Volume: 104 Pages: 98-105
  • DOI: 10.1016/j.lungcan.2016.12.017
  • Peer Reviewed
• [Journal Article] Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma. (2017)
  • Author(s): Wu D, Hiroshima K, Yusa T, Ozaki D, Koh E, Sekine Y, Matsumoto S, Nabeshima K, Sato A, Tsujimura T, Yamakawa H, Tada Y, Shimada H, Tagawa M.
  • Journal Title: Ann Diagn Pathol Volume: 26 Pages: 31-37
  • DOI: 10.1016/j.anndiagpath.2016.10.010
  • Peer Reviewed
• [Journal Article] High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma (2016)
  • Author(s): Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, Hasegawa S, Nakano T, Nasu M, Pastorino S, Szymiczek A, Bononi A, Tanji M, Pagano I, Gaudino G, Napolitano A, Goparaju C, Pass HI, Yang H, Carbone M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 113 Pages: 13432-13437
  • DOI: 10.1073/pnas.1612074113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests. (2016)
  • Author(s): Hida T, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Iwasaki A, Okamoto T, Oda Y, Honda H, Nabeshima K.
  • Journal Title: Pathol Int. Volume: 66 Pages: 563-570
  • DOI: 10.1111/pin.12453
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Low homozygous/high heterozygous deletion status by p16 FISH correlates with a better prognostic group than high homozygous deletion status in malignant pleural mesothelioma. (2016)
  • Author(s): Hamasaki M, Matsumoto S, Abe S, Hamatake D, Kamei T, Hiroshima K, Kawahara K, Sato A, Tsujimura T, Nakatani Y, Yoshida Y, Iwasaki A, Nabeshima K.
  • Journal Title: Lung Cancer Volume: 99 Pages: 155-161
  • DOI: 10.1016/j.lungcan.2016.07.011
  • Peer Reviewed
• [Journal Article] Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level (2015)
  • Author(s): Emi M et al
  • Journal Title: J Hum Genet Volume: 60 Pages: 647-649
  • DOI: 10.1038/jhg.2015.91
  • NAID: 40020621530
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 悪性胸膜中皮腫の診断におけるBAP1免疫染色の有用性の検討 (2017)
  • Author(s): 佐藤鮎子，篠原義康，阿部晋也，鍋島一樹，辻村 亨
  • Organizer: 第106回日本病理学会総会
• [Presentation] 悪性中皮腫細胞株におけるヒドロキシクロロキンの細胞致死効果についての検討 (2017)
  • Author(s): 篠原義康，佐藤鮎子，阿部晋也，辻村亨
  • Organizer: 第106回日本病理学会総会
• [Presentation] 中皮腫診断の最前線 (2017)
  • Author(s): 鍋島一樹，木下義晃，松本慎二，樋田知之，佐藤鮎子，辻村 亨，河原邦光，廣島健三，亀井敏昭，小田 義直
  • Organizer: 第106回日本病理学会総会
• [Presentation] 243症例の悪性胸膜中皮腫の統合的ゲノム解析 (2017)
  • Author(s): 竹下純平, 山本尚吾, 辰野健二, 白石友一, 大搗泰一郎, 栗林康造, 近藤展行, 長谷川誠紀, 佐藤鮎子, 辻村亨, 中野孝司, 関戸好孝, 油谷浩幸
  • Organizer: 第76回日本癌学会総会
• [Presentation] 悪性胸膜中皮腫の胸水細胞診におけるBAP1免疫染色の有用性 (2017)
  • Author(s): 辻村 亨，佐藤鮎子，隅田安由美，篠原義康，阿部晋也
  • Organizer: 第58 回日本臨床細胞学会総会春期大会
• [Presentation] 中皮腫の早期診断に役立つp16 FISHとBAP1, MTAP免疫染色 (2017)
  • Author(s): 鍋島一樹，木下義晃，松本慎二，樋田知之，佐藤鮎子，辻村 亨，河原邦光，廣島健三，亀井敏昭，小田義直
  • Organizer: 第58回日本臨床細胞学会総会春期大会
• [Presentation] Utility of liquid-based cytology in the diagnosis of malignant pleural mesothelioma (2016)
  • Author(s): Tsujimura T, Sato A, Shinohara Y, Sumida A, Nakanishi T, Sato G, Ishida M, Torii Y, Shimizu S.
  • Organizer: The 19th International Congress of Cytology
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-05-30
  • Int'l Joint Research
• [Presentation] Clinical, cytological, and molecular biological approaches to the diagnosis of early mesothelioma (2016)
  • Author(s): Tsujimura T, Sato A, Shinohara Y, Sumida A, Hasegawa S, Nakano T.
  • Organizer: The 19th International Congress of Cytology
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-05-30
  • Int'l Joint Research
• [Presentation] 悪性胸膜中皮腫における液状化検体細胞診の有用性の検討 (2016)
  • Author(s): 佐藤鮎子, 篠原義康, 清水重喜, 隅田安由美, 中野孝司, 長谷川誠紀, 鍋島一樹, 辻村 亨
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（仙台）
  • Year and Date: 2016-05-13
• [Presentation] 悪性中皮腫細胞株におけるオートファジーの役割 (2016)
  • Author(s): 篠原義康, 佐藤鮎子, 隅田安由美, 辻村 亨
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（仙台）
  • Year and Date: 2016-05-12
• [Presentation] Relationship of PD-L1 Expression and Prognosis in Epithelioid Mesothelioma (2016)
  • Author(s): Tsujimura T, Kudo T, Shinohara Y, Sato A, Shimizu S, Daimon T, Hasegawa S, Nakano T.
  • Organizer: 13th International Conference of the International Mesothelioma Interest Group
  • Place of Presentation: Birmingham, UK
  • Year and Date: 2016-05-03
  • Int'l Joint Research
• [Presentation] NF2遺伝子関連蛋白Merlinの染色性と中皮腫の腫瘍特性の関連 (2015)
  • Author(s): 栗林康造, 家城隆次, 大搗泰一郎, 金村晋吾, 柴田英輔, 政近江利子, 神谷 瞳, 三上浩司, 寺田貴普, 近藤展行, 佐藤鮎子, 清水重喜, 長谷川誠紀, 辻村 亨, 中野孝司
  • Organizer: 第56回日本肺癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2015-11-28
• [Presentation] 中皮腫診断の現状と将来 (2015)
  • Author(s): 辻村 亨, 佐藤鮎子, 篠原義康, 工藤朝雄, 今橋祐喜, 清水重喜, 鍋島一樹, 長谷川誠紀, 中野孝司
  • Organizer: 第56 回日本臨床細胞学会総会春期大会
  • Place of Presentation: 松江テルサ（松江）
  • Year and Date: 2015-06-13
• [Presentation] 胸水検体を用いた悪性胸膜中皮腫の分子病理学的診断法の検討 (2015)
  • Author(s): 佐藤鮎子，篠原義康，工藤朝雄，今橋祐喜，中野孝司，長谷川誠紀，辻村亨
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-04-30
• [Presentation] 悪性中皮腫における上皮間葉転換分子TWIST1の生物学的作用 (2015)
  • Author(s): 篠原義康，佐藤鮎子，工藤朝雄，今橋祐喜，中野孝司，長谷川誠紀，辻村亨
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-04-30
• [Presentation] 悪性胸膜中皮腫におけるPD-L1発現と予後との関連性 (2015)
  • Author(s): 工藤朝雄，今橋祐喜，佐藤鮎子，篠原義康，鍋島一樹，中野孝司，長谷川誠紀，辻村亨
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-04-30
• [Book] 石綿関連疾患の病理とそのリスクコミュニケーション (2015)
  • Author(s): 清水重喜，鳥井郁子，佐藤鮎子，辻村 亨
  • Total Pages: 300
  • Publisher: 篠原出版新社