Cytological and molecular analysis of malignant mesothelioma cells and identification of its cancer stem cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590935
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hyogo College of Medicine
• Principal Investigator: FUJIMORI Yoshihiro Hyogo College of Medicine, 医学部, 准教授 (20229058)
• Co-Investigator(Kenkyū-buntansha): NAKANO Takashi 兵庫医科大学, 医学部, 教授 (10155781)
• Project Period (FY): 2008 – 2010
• Keywords: 中皮腫 / アポトーシス / 幹細胞

Research Abstract

Malignant mesothelioma is an aggressive tumor of serosal surfaces which is refractory to current treatment options. We analyzed cytological and molecular characteristics of mesothelioma cells to identify the stem cells that initiate its tumorogenesis. We first analyzed the apoptosis of mesothelioma cells induced by arsenic trioxide (As_2O_3), which is used clinically to treat acute promyelocytic leukemia. We found that As_2O_3 inhibited cell viability of a mesothelioma cell line, NCI-H2052. As_2O_3 induced apoptosis of NCI-H2052 cells, which was accompanied by activation of JNK1/2, ERK1/2 and caspase-3. As_2O_3 induced apoptosis of NCI-H2052 cells mainly through JNK1/2 activation, and ERK1/2 was involved in As_2O_3-induced apoptosis when JNK1/2 was inactivated. On the other hands, we found that PP2, a selective SFK inhibitor, induced apoptosis through a caspase-8 pathway in NCI-H28 cells which are resistant to As_2O_3. Fyn-deficiency is prerequisite for caspase-8-dependent apoptosis induced by SFK inhibitors in mesothelioma cells. In our search for cancer stem cells, we found that mesothelioma cells expressed CD318, which play a role in mesotheiloma.

Research Products

• [Journal Article] Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. (2011)
  • Author(s): Eguchi R, Fujimori Y, Takeda H, Tabata C, Ohta T, Kuribayashi K, Fukuoka K, Nakano T
  • Journal Title: Journal of Cellular Physiology 226 Pages: 762
  • Peer Reviewed
• [Journal Article] CD318/CUB-domain-containing protein 1 expression on cord blood hematopoietic progenitors. (2010)
  • Author(s): Takeda H, Fujimori Y, Kai S, Ogawa H, Nakno T
  • Journal Title: Experimental and Therapeutic Medicine. 1 Pages: 497-501
  • Peer Reviewed
• [Presentation] 悪性中皮腫において亜ヒ酸はJNKおよびERKを介したアポトーシスを誘導する (2010)
  • Author(s): 江口良二,藤盛好啓,田端千春,栗林康造,福岡和也,中野孝司
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-29
• [Presentation] Fyn低発現型の悪性中皮腫においてPP2はアポトーシスを誘導する (2010)
  • Author(s): 江口良二,藤盛好啓,久保秀司,田端千春,栗林康造,福岡和也,中野孝司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 悪性胸膜中皮腫におけるangiopoietin (Ang)-1の臨床的新規役割について (2010)
  • Author(s): 田端千春,田端理英,栗林康造,福岡和也,江口良二,藤盛好啓,中野孝司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Frequent deletions in 3p21.1 region in malignant mesothelioma cell lines established from Japanese patients. (2010)
  • Author(s): Yoshikawa Y, Nakano T, Sato A, Fukuoka K, Murakami A, Yamada S, Kuribayashi K, Tabata C, Fujimori Y, Morinaga T, Tsujimura T, Hashimoto-Tamaoki T
  • Organizer: The 10th International Conference of the International Mesothelioma Interest Group
  • Place of Presentation: Kyoto
  • Year and Date: 2010-09-01
• [Presentation] Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. (2010)
  • Author(s): Eguchi R, Fujimori Y, Tabata C, Kuribayashi K, Fukuoka K, Nakano T
  • Organizer: 10th International Conference of International Mesothelioma Interest Group (IMIG)
  • Place of Presentation: Kyoto
  • Year and Date: 2010-08-31
• [Presentation] Heme oxigenase-1 promotor polymorphism is associated with risk of malignant pleural mesothelioma. (2009)
  • Author(s): Murakami A, Fujimori Y, Yoshikawa Y, Tamaoki T, Iida S, Tamura K, Kuribayashi K, Tabata C, Fukuoka K, Nakano T
  • Organizer: 14th Congress of the Asian Pacific Society Respirology
  • Place of Presentation: Seoul
  • Year and Date: 2009-11-14
• [Presentation] 悪性中皮腫株NCI-H2052において亜砒酸により誘導されるアポトーシスのキータンパク質はJNKである (2009)
  • Author(s): 江口良二,藤盛好啓,栗林康造,福岡和也,中野孝司
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Arsenic trioxide induces apoptosis of human malignant mesothelioma cells through induction of reactive oxygen species. (2009)
  • Author(s): Hirayama N, Eguchi R, Fujimori Y, Muramoto M, Okada A, Kuribayashi K, Fukuoka K, Tsubota N, Nakano T
  • Organizer: 13th World Conference on Lung Cancer
  • Place of Presentation: San Francisco
  • Year and Date: 2009-07-31
• [Presentation] 亜砒酸はヒト悪性中皮腫細胞にアポトーシスを誘導する (2008)
  • Author(s): 江口良二,藤盛好啓,村元正和,栗林康造,福岡和也,中野孝司
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28