In vivo observation of stemness acquisition in differentiated cancer cells

• Project/Area Number: 25670177
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: KUNIYASU Hiroki 奈良県立医科大学, 医学部, 教授 (00253055)
• Co-Investigator(Kenkyū-buntansha): KITADAI Yasuhiko 広島大学, 医歯薬学大学院, 准教授 (10304437) ; CHIHARA Yoshitomo 奈良県立医科大学, 医学部, 講師 (40405395) ; FUJIMOTO Yoshio 奈良県立医科大学, 医学部, 教授 (90192731)
• Co-Investigator(Renkei-kenkyūsha): TAKAKI Miyako 奈良県立医科大学, 医学部, 特任教授 (00033358)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: がん幹細胞 / 幹細胞分化 / キネティクス / がん細胞分化・脱分化 / 多光子励起蛍光顕微鏡 / 冬眠性がん幹細胞 / 増殖性がん幹細胞 / 分化がん細胞 / 幹細胞可塑性

Outline of Final Research Achievements

Dedifferentiation or acquisition of stemness was examined in mouse cancer cells. Expression of CD133 and nucleostemin in CT26 cells showed that differentiations of dormant cancer stem (DCS) to proliferating cancer stem (PCS) and PCS to differentiated cancer cells (DCC) were found in 3.5% and 5.6%, respectively. In contrast, dedifferentiations of DCC to PCS and PCS to DCS were found in 1.7% and 1%, respectively. In in vivo observation of KT-5 cells in mouse brain showed stem-related ALP activity was disappeared in 16%, whereas appeared in 1%. These findings suggest that the dedifferentiation or acquisition of stemness might be a common phenomenon in cancer. The biological meaning and clinical importance should be examined in further studies.

Research Products

• [Journal Article] High motility group box 1 induces cancer aggressiveness and drug resistance. (2015)
  • Author(s): Ohmori H, Luo Y, Fujii K, Sasaki T, Kuniyasu H
  • Journal Title: Annals of Clinical Pathology Volume: 3(1) Pages: 1042-1042
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alteration of the plasma free amino acids profiles in cancer patients is associated with dysregulated metabolism in skeletal muscle (2015)
  • Author(s): Luo Y, Yoneda J, Sasaki T, Kawahara I, Goto K, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Archives of Cancer Research Volume: 3(1) Pages: 5-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AKT plays a crucial role in gastric cancer. (2015)
  • Author(s): Sasaki T, Yamashita Y, Kuniyasu H
  • Journal Title: Oncology Letters Volume: in press
  • NAID: 120005976143
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 18F-fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in oral squamous cell carcinoma. (2015)
  • Author(s): Shimomura H, Sasahira T, Yamanaka Y, Kurihara M, Imai Y, Tamaki S, Yamakawa N, Shirone N, Hasegawa M, Kuniyasu H, Kirita T
  • Journal Title: International Journal of Clinical Oncology Volume: 20(2) Issue: 2 Pages: 308-316
  • DOI: 10.1007/s10147-014-0711-5
  • Peer Reviewed / Open Access
• [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model (2015)
  • Author(s): Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
  • Journal Title: J Virol Volume: 89 Issue: 9 Pages: 4866-4879
  • DOI: 10.1128/jvi.03676-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after transection of the gut in rodents. (2015)
  • Author(s): Goto K, Kawahara I, Kuniyasu H, Takaki M
  • Journal Title: J Physiol Sci Volume: 未定 Issue: 4 Pages: 377-383
  • DOI: 10.1007/s12576-015-0377-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Update of molecular pathobiology in oral cancer: a review. (2014)
  • Author(s): Sasahira T, Kirita T, Kuniyasu H.
  • Journal Title: International Journal of Clinical Oncology Volume: 19 Issue: 3 Pages: 431-436
  • DOI: 10.1007/s10147-014-0684-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Significance of AKT in gastric cancer. (2014)
  • Author(s): Sasaki T, Kuniyasu H
  • Journal Title: International Journal of Oncology Volume: 45(6) Issue: 6 Pages: 2187-2192
  • DOI: 10.3892/ijo.2014.2678
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer. (2014)
  • Author(s): Sasaki T, Ohmori H, et al
  • Journal Title: Pathobiology Volume: 81 Issue: 1 Pages: 36-41
  • DOI: 10.1159/000351721
  • Peer Reviewed / Open Access
• [Journal Article] Possible peripheral mechanism for taste disorder in S-1 administered rats. (2014)
  • Author(s): Aoki K, Obata K, Kurihara M, Kuniyasu H, Kirita T, Takaki M
  • Journal Title: Int J Clin Oncol Volume: 19 Issue: 3 Pages: 549-556
  • DOI: 10.1007/s10147-013-0572-3
  • Peer Reviewed
• [Journal Article] Cancer usurps skeletal muscle as an energy repository (2014)
  • Author(s): Luo Y, Ohmori H, et al
  • Journal Title: Cancer Res Volume: 74 Issue: 1 Pages: 330-340
  • DOI: 10.1158/0008-5472.can-13-1052
  • Peer Reviewed / Open Access
• [Journal Article] Prox1 and FOXC2 Act as Regulators of Lymphangiogenesis and Angiogenesis in Oral Squamous Cell Carcinoma (2014)
  • Author(s): Sasahira T, Ueda N, Yamamoto K, Kurihara M, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H
  • Journal Title: PLoS One Volume: 9(3) Issue: 3 Pages: e92534-e92534
  • DOI: 10.1371/journal.pone.0092534
  • Peer Reviewed / Open Access
• [Journal Article] Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas (2014)
  • Author(s): Kuwada M, Kuniyasu H, et al
  • Journal Title: BMC Res Note Volume: 7 Issue: 1 Pages: 203-203
  • DOI: 10.1186/1756-0500-7-203
  • Peer Reviewed / Open Access
• [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression. (2014)
  • Author(s): Zhou L, Luo Y, Sato S, Tanabe E, Kitayoshi M, Fujiwara R, Sasaki T, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Pathobiology Volume: 81(4) Issue: 4 Pages: 169-175
  • DOI: 10.1159/000362092
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method (2014)
  • Author(s): Shunsuke Shinmei, Kazuhiro Sentani, Tetsutaro Hayashi, Naoya Sakamoto, Keisuke Goto, Htoo Zarni Oo, Yutaka Naito, Jun Teishima, Akio Matsubara, Naohide Oue, Hiroki Kuniyasu, Wataru Yasui
  • Journal Title: Urologic Oncology Volume: 32 Issue: 6 Pages: 769-778
  • DOI: 10.1016/j.urolonc.2014.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Serum CD10 is associated with liver metastasis in colorectal cancer. (2014)
  • Author(s): Sasaki T, Kuniyasu H, Luo Y, Fujiwara R, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y
  • Journal Title: Journal of Surgical Research Volume: 192 Issue: 2 Pages: 390-394
  • DOI: 10.1016/j.jss.2014.05.071
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transport and Golgi organisation protein 1 is a novel tumour progressive factor in oral squamous cell carcinoma (2014)
  • Author(s): Sasahira T, Kirita T, Yamamoto K, Ueda N, Kurihara M, Matsushima S, Bhawal UK, Bosserhoff AK, Kuniyasu H
  • Journal Title: Eur J Cancer Volume: 50 Issue: 12 Pages: 2142-2151
  • DOI: 10.1016/j.ejca.2014.05.006
  • Peer Reviewed / Open Access
• [Journal Article] HuD promotes progression of oral squamous cell carcinoma (2014)
  • Author(s): Sasahira T, Kurihara M, Yamamoto K, Ueda N, Nakashima C, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H
  • Journal Title: Pathobiology Volume: 81 Issue: 4 Pages: 206-214
  • DOI: 10.1159/000366022
  • Peer Reviewed / Open Access
• [Journal Article] Development of an anti-claudin-3 and -4 bispecific monoclonal antibody for cancer diagnosis and therapy (2014)
  • Author(s): Xiangru Li, Manami Iida, Minoru Tada, Akihiro Watari, Yumi Kawahigashi, Yuka Kimura, Taku Yamashita, Akiko Ishii-Watabe, Tadayuki Uno, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
  • Journal Title: J Pharmacol Exp Ther Volume: 351 Issue: 1 Pages: 206-213
  • DOI: 10.1124/jpet.114.216911
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of two types of angiotensin II receptors in colorectal carcinoma progression (2014)
  • Author(s): Zhou L, Kuniyasu H, et al.
  • Journal Title: Pathobiology Volume: in press
  • Peer Reviewed
• [Journal Article] Identification of PRL1 as a Novel Diagnostic and Therapeutic Target for Castration Resistant Prostate Cancer by the Escherichia Coli Ampicillin Secretion Trap (CAST) Method. (2014)
  • Author(s): Shinmei S, Kuniyasu H, et al.
  • Journal Title: Urologic Oncology Seminar and Volume: in press
  • Peer Reviewed
• [Journal Article] Multiple roles of angiotensin in colorectal cancer (2013)
  • Author(s): Kuniyasu H
  • Journal Title: World J Clin Oncol Volume: 3 Issue: 12 Pages: 150-154
  • DOI: 10.5306/wjco.v3.i12.150
  • Peer Reviewed
• [Journal Article] The role of epidermal growth factor receptor in cancer metastasis and microenvironment. (2013)
  • Author(s): Sasaki T, Kuniyasu H
  • Journal Title: Biomed Res Int Volume: 2013 Pages: 546318-546318
  • DOI: 10.1155/2013/546318
  • Peer Reviewed
• [Journal Article] Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma (2013)
  • Author(s): Sasahira T, Ueda N, Yamamoto K, Bhawal UK, Kurihara M, Kirita T, Kuniyasu H
  • Journal Title: Clinical Experimental Metastasis Volume: 30(2) Issue: 2 Pages: 165-176
  • DOI: 10.1007/s10585-012-9525-x
  • Peer Reviewed
• [Journal Article] High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Eur J Cancer Volume: 49 Issue: 3 Pages: 741-751
  • DOI: 10.1016/j.ejca.2012.09.016
  • Peer Reviewed
• [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma. (2013)
  • Author(s): Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
  • Journal Title: Hum Pathol Volume: in press Issue: 6 Pages: 1098-1106
  • DOI: 10.1016/j.humpath.2012.09.016
  • Peer Reviewed
• [Journal Article] In vivo imaging of enteric neurogenesis in the deep tissue of mouse smallintestine. hearts of SERCA2a transgenic rats. (2013)
  • Author(s): Goto K, Obata K, Takaki M, 他
  • Journal Title: PLoS ONE Volume: 8 Issue: 1 Pages: e54814-e54814
  • DOI: 10.1371/journal.pone.0054814
  • Peer Reviewed
• [Journal Article] Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma. (2013)
  • Author(s): Kurihara M, Kirita T, Sasahira T, Ohmori H, Matsushima S, Yamamoto K, Bosserhoff AK, Kuniyasu H
  • Journal Title: Br J Cancer Volume: 108 Issue: 7 Pages: 1460-9
  • DOI: 10.1038/bjc.2013.27
  • Peer Reviewed
• [Journal Article] Diagnostic markers of urothelial cancer based on DNA methylation analysis. (2013)
  • Author(s): Chihara Y, Kuniyasu H, et al.
  • Journal Title: BMC Cancer Volume: 13 Issue: 1 Pages: 275-275
  • DOI: 10.1186/1471-2407-13-275
  • Peer Reviewed
• [Journal Article] Increased phosphorylation of AKT in high-risk gastric mucosa (2013)
  • Author(s): Sasaki T, Kuniyasu H, et al
  • Journal Title: Anticancer Res Volume: 33 Pages: 3295-3300
  • Peer Reviewed
• [Presentation] 鉄－アルミニウム新規合金素材を発熱体とする磁気温熱療法のマウス皮下腫瘍モデルを用いた検証 (2015)
  • Author(s): 國安弘基
  • Organizer: 第5回磁気ハイパーサーミア研究会
  • Place of Presentation: 奈良市
  • Year and Date: 2015-01-20
  • Invited
• [Presentation] 損傷した消化管壁内神経の再生新生 (2014)
  • Author(s): 高木 都、後藤 桂、川原 勲、鍋倉淳一、國安弘基
  • Organizer: 第16回日本神経消化器病学会
  • Place of Presentation: 東京都
  • Year and Date: 2014-11-06 – 2014-11-07
  • Invited
• [Presentation] Claudin-4を標的とする治療の可能性 (2014)
  • Author(s): 國安弘基、羅 奕、千原良友、桑田真臣、北吉美沙穂、田邊絵里子、佐々木隆光、大森 斉、近藤昌夫
  • Organizer: 第29回発癌病理研究会
  • Place of Presentation: いわき市
  • Year and Date: 2014-09-01 – 2014-09-03
• [Presentation] メタボリック症候群における大腸癌 (2014)
  • Author(s): 國安弘基
  • Organizer: 第103回日本病理学会総会ワークショップ
  • Place of Presentation: 広島市
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] 癌細胞はHMGB1を介して筋組織をエネルギー源として利用している (2013)
  • Author(s): 國安弘基ほか
  • Organizer: 第28回発癌病理学会シンポジウム
  • Place of Presentation: 南城市
• [Presentation] 新規MIA gene familyであるMIA2の口腔癌における機能解析 (2013)
  • Author(s): 笹平智則、國安弘基ほか
  • Organizer: 第24回日本臨床口腔病理学会、若手シンポジウム「新しきパラダイムを求めて」
  • Place of Presentation: 東京都
• [Presentation] 口腔癌におけるピルビン酸キナーゼ作用の多様性 (2013)
  • Author(s): 栗原都、國安弘基ほか
  • Organizer: 第24回日本消化器癌発生学会、シンポジウム「がんの代謝特性とがん生物学」
  • Place of Presentation: 金沢市
• [Presentation] Effect of intermittent calorie restriction on cancer stem cells. (2013)
  • Author(s): Luo Y, Kuniyasu H, et al
  • Organizer: 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington DC
• [Presentation] HMGB1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Kuniyasu H, et al
  • Organizer: Merinoff World Congress 2013:HMGB1
  • Place of Presentation: New York
• [Presentation] Merinoff World Congress 2013:HMGB1 (2013)
  • Author(s): Luo Y, Kuniyasu H et al
  • Organizer: The 18th Japan-Korea Cancer Research Workshop
  • Place of Presentation: Gifu
  • Invited
• [Presentation] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer. (2013)
  • Author(s): Luo Y, Kuniyasu H, et al
  • Organizer: 4th JCA-AACR Special Joint Conference －The Latest Advances in Gastric Cancer Research: From Basic Science to Therapeutics－
  • Place of Presentation: Urayasu
• [Presentation] Fabrication process and magnetocaloric property of aluminum based beads dispersed ferromagnetic particles for magnetic hyperthermia cancer care (2013)
  • Author(s): Kodama K, Kuniyasu H, et al
  • Organizer: 4th TSME International Conference on Mechanical Engineering
  • Place of Presentation: Pattaya, Chonburi
• [Presentation] Development of claudin-4–specific monoclonal antibodies and their anti-tumor activities. (2013)
  • Author(s): Iida M, Kuniyasu H, et al
  • Organizer: 24th Antibody Engineering & Therapeutics
  • Place of Presentation: Huntington Beach, CA, USA
• [Book] Current Research in Cancer 9‐Non-functioning neuroendocrine tumor of the pancreas- clinical implication. (2015)
  • Author(s): Sasaki T, Kuniyasu H
  • Total Pages: 165
  • Publisher: Research Media, Kerala, India
• [Book] Current Research in Cancer 9‐Impact of trans fatty acids on colorectal cancer (2015)
  • Author(s): Kuniyasu H, Sasaki T, Fujii K, Ohmori H
  • Total Pages: 165
  • Publisher: Research Media, Kerala, India
• [Book] Current Research in Cancer 8-Significance of AKT in gastric cancer (2014)
  • Author(s): Sasaki T, Yamashita Y, Kuniyasu H
  • Total Pages: 156
  • Publisher: Research Media, Kerala, India
• [Book] Current Research in Cancer 8-Significance and the cause of alteration of the plasma free amino acids profiles in cancer (2014)
  • Author(s): Kuniyasu H, Luo Y, Yoneda J, Sasaki T, Fujii K, Ohmori H
  • Total Pages: 156
  • Publisher: Research Media, Kerala, India
• [Book] Current Research in Cancer 7 (2013)
  • Author(s): Kuniyasu H, et al
  • Total Pages: 215
  • Publisher: Research Media
• [Book] Current Research in Cancer 7 (2013)
  • Author(s): Sasaki t, Kuniyasu H, et al
  • Total Pages: 215
  • Publisher: Research Media
• [Remarks] 奈良県立医科大学分子病理学講座
  • URL: http://www.naramed-u.ac.jp/~molepath/
• [Patent(Industrial Property Rights)] クラウディン（CLDN）４抗体、その抗体のフラグメント、その抗体を含む医薬組成物、CLDN４エピトープに結合する分子、及び腫瘍マーカーに関する発明 (2014)
  • Inventor(s): 國安弘基ほか
  • Industrial Property Rights Holder: 國安弘基ほか
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-036111
  • Filing Date: 2014-02-27
  • Overseas