Study on new approach to effective acquirement and the maintaining mechanisms of prostate cancer stem cell.

• Project/Area Number: 22390070
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: KONISHI Noboru 奈良県立医科大学, 医学部, 教授 (20145832)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Keiji 奈良県立医科大学, 医学部, 講師 (90336850)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 前立腺 / 癌幹細胞 / 癌化 / CD133 / CD44 / syndecan-1 / 前立腺癌 / quiecence / Syndecan-1 / 抗癌剤ストレス

Research Abstract

Increasing evidence suggests that tumor-initiating cells (TIC) contribute to the development of prostate cancer. We identify syndecan-1 as a key molecule for maintaining the stability of prostate cancer TIC. Holoclones harboring biological properties of stemness overexpressed syndecan-1, but showed reduced expression of NADPH oxidase and synthesis of hydrogen peroxide and oxygen radicals. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer, early intervention with a syndecan-1 inhibitor (OGT2115) or syndecan-1 RNAi reduced the cancer incidence and the number of c-kit+/CD44+ cells. Syndecan-1 immunopositivity in prostate cancer cells was significantly associated with biochemical recurrence after radical prostatectomy. Taken together, syndecan-1 contributes to prostatic carcinogenesis by maintaining TIC, and might be a novel target molecule for effective cancer therapy.

Research Products

• [Journal Article] Calculated Tumor Volume Is an Independent Predictor of Biochemical Recurrence in patients Who Underwent Retropubic Radical Prostatectomy (2012)
  • Author(s): Tanaka, N., Fujimoto, K., Hirayama, A., Nakai, Y., Chihara, Y., Anai, S., Tomioka, A., Shimada, K., Konishi, N., Hirao, Y
  • Journal Title: Advance in Urology
  • Peer Reviewed
• [Journal Article] Phyllodes tumor of the prostate (2012)
  • Author(s): Fujii, T., Shimada, K., Tanaka, N., Fujimoto, K., Konishi, N
  • Journal Title: Pathol Int Volume: 62(3) Pages: 204-208
  • NAID: 10031185190
  • Peer Reviewed
• [Journal Article] Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion (2012)
  • Author(s): Asai, O., Nakatani, K., Konishi, N.
  • Journal Title: Kidney Int Volume: 81 Pages: 539-547
  • Peer Reviewed
• [Journal Article] CD138 を介する前立腺癌進展メカニズムの解析-tumor initiating cellsへの影響- (2012)
  • Author(s): 島田啓司、藤井智美、穴井智、藤本清秀、小西 登
  • Journal Title: 泌尿器外科 Volume: 25 Pages: 1597-1600
  • Peer Reviewed
• [Journal Article] Calculated tumor volume is an independent predictor of biochemical recurrence in patients who underwent retropubic radical prostatectomy. (2012)
  • Author(s): Tanaka, N., Fujimoto, K., Hirayama, A., Nakai, Y., Chihara, Y., Anai, S., Tomioka, A., Shimada, K., Konishi, N., Hirao, Y.
  • Journal Title: Advance in Urology Volume: 2012 Pages: 7-7
  • DOI: 10.1155/2012/204215
  • Peer Reviewed
• [Journal Article] Phyllodes tumor of the prostate. (2012)
  • Author(s): Fujii, T., Shimada, K., Tanaka, N., Fujimoto, K., Konishi, N.
  • Journal Title: Pathol Int Volume: 62 Pages: 204-208
  • DOI: 10.1111/j.1440-1827.2012.02796.x
  • NAID: 10031185190
  • Peer Reviewed
• [Journal Article] Decreased renal alpha-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. (2012)
  • Author(s): Asai O, Nakatani K, Tanaka T, Sakan H, Imura A, Yoshimoto S, Samejima K, Yamaguchi Y, Matsui M, Akai Y, Konishi N, Iwano M, Nabeshima Y, Saito Y
  • Journal Title: Kidney Int. Volume: 81(6) Pages: 539-47
  • DOI: 10.1038/ki.2011.423
  • Peer Reviewed
• [Journal Article] CD138を介する前立腺癌進展メカニズムの解析 －tumor initiating cellsへの影響－ (2012)
  • Author(s): 島田啓司、藤井智美、穴井智、藤本清秀、小西 登
  • Journal Title: 泌尿器外科 Volume: 25 Pages: 1597-1600
  • Peer Reviewed
• [Journal Article] Direct targeting of fibroblast growth factor-inducible 14 protein protects against renal ischemia reperfusion injury (2011)
  • Author(s): Hotta, K., Sho, M., Yamato, I., Shimada, K., Harada, H., Akahori, T., Nakamura, S., Konishi, N., Yagita, H., Nonomura, K., Nakajima, Y
  • Journal Title: Kidney Int Volume: 79 Pages: 151-153
  • Peer Reviewed
• [Journal Article] 前立腺癌-基礎・臨床研究のアップデート- I .基礎 前立腺癌の病理 TNM 分類と取扱い規約の諸問題 (2011)
  • Author(s): 島田啓司,小西 登
  • Journal Title: 日本臨牀 Volume: 69 Pages: 31-35
• [Journal Article] ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer (2011)
  • Author(s): Tasaki. M., Shimada. K., Kimura. H., Tsujikawa. K., Konishi. N
  • Journal Title: Br J Cancer Volume: 104 Pages: 700-706
  • Peer Reviewed
• [Journal Article] 放射線抵抗性前立腺癌に対する分子標的治療の試み (2011)
  • Author(s): 穴井 智, 井上剛志, 池田朋博, 三宅牧人, 千原良友, 田中宣道, 藤本清秀, 平尾佳彦, 島田啓司, 小西 登
  • Journal Title: 泌尿器外科 Volume: 24 Pages: 1263-1265
  • Peer Reviewed
• [Journal Article] Effects of minocycline on hind-limb motor function and gray and white matter injury after spinal cord ischemia in rats (2011)
  • Author(s): Takeda, M., Kawaguchi, M., Kumatoriya, T., Horiuchi, T., Watanabe, K., Inoue, S., Konishi, N., Furuya, H
  • Journal Title: Spine Volume: 36 Pages: 1919-1924
  • NAID: 10030901085
  • Peer Reviewed
• [Journal Article] Risk-stratified survival rates and predictors of biochemical recurrence after radical prostatectomy in a Nara, Japan, cohort study (2011)
  • Author(s): Tanaka, N., Fujimoto, K., Hirayama, A., Torimoto, K., Okajima, E., Tanaka, M., Miyake, M., Shimada, K., Konishi, N., Hirao, Y
  • Journal Title: Int J Clin Oncol Volume: 16 Pages: 553-559
  • NAID: 10030246925
  • Peer Reviewed
• [Journal Article] Prognostic significance of CD45RO+ memory T cells in renal cell carcinoma (2011)
  • Author(s): Hotta, K., Sho, M., Fujimoto, K., Shimada, K., Yamato, I., Anai, S., Konishi, N., Hirao, Y., Nonomura, K., Nakajima, Y
  • Journal Title: Br J Cancer Volume: 105 Pages: 1191-1196
  • Peer Reviewed
• [Journal Article] Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2alpha contributes to human bladder cancer cell survival (2011)
  • Author(s): Shimada, K., Anai, S., Marco DA, Fujimoto, K., Konishi, N
  • Journal Title: BMC Urol
  • Peer Reviewed
• [Journal Article] Risk-stratified survival rates and predictors of biochemical recurrence after radical prostatectomy in a Nara, Japan, cohort study (2011)
  • Author(s): Tanaka, N., Fujimoto, K., Konishi, N., et al
  • Journal Title: Int J Clin Oncol Volume: 16巻 Pages: 553-559
  • NAID: 10030246925
  • Peer Reviewed
• [Journal Article] Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2alpha contributes to human bladder cancer cell survival (2011)
  • Author(s): Shimada, K., Konishi, N., et al
  • Journal Title: BMC Urol Volume: VOL.11 Pages: 8-8
  • Peer Reviewed
• [Journal Article] 前立腺癌(第2版)-基礎・臨床研究のアップデート-I.基礎前立腺癌の病理TNM分類と取扱い規約の諸問題 (2011)
  • Author(s): 島田啓司, 小西登
  • Journal Title: 日本臨牀 Volume: 69巻 Pages: 31-35
  • Peer Reviewed
• [Journal Article] Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma (2010)
  • Author(s): Shimada, K., Nakamura, M., De Velasco MA, Tanaka, M., Ouji, Y., Miyake, M., Fujimoto, K., Hirao, K., Konishi, N
  • Journal Title: Cancer Sci Volume: 101 Pages: 155-160
  • NAID: 10027199949
  • Peer Reviewed
• [Journal Article] Posttreatment but not pretreatment with selective beta-adrenoreceptor 1 antagonists provides neuroprotection in the hippocampus in rats subjected to transient forebrain ischemia (2010)
  • Author(s): Iwata, M., Inoue, S., Kawaguchi, M., Nakamura, M., Konishi, N., Furuya, H
  • Journal Title: Anesth Analg Volume: 110 Pages: 1126-1132
  • Peer Reviewed
• [Journal Article] 第11 章 尿管・膀胱・尿道 乳頭腫 (2010)
  • Author(s): 島田啓司, 小西 登
  • Journal Title: 病理と臨床 Volume: 28 Pages: 210-211
• [Journal Article] 第12 章 男性生殖器 神経周囲浸潤 (2010)
  • Author(s): 小西 登
  • Journal Title: 病理と臨床 Volume: 28 Pages: 236-237
• [Journal Article] Syndecan-1(CD138)を介した前立腺癌進展メカニズム (2010)
  • Author(s): 島田啓司, 小西 登
  • Journal Title: 泌尿器外科 Volume: 23 Pages: 1011-1014
  • Peer Reviewed
• [Journal Article] ステージC前立腺癌症例における根治的前立腺全摘除術、外部照射放射線治療およびホルモン治療の治療成績 (2010)
  • Author(s): 田中宣道, 冨岡厚志, 仲川嘉紀, 林美樹, 百瀬均, 三馬省二, 岡島英二郎, 藤本清秀, 平尾佳彦, 浅川勇雄, 玉本哲郎, 長谷川正俊, 小西 登
  • Journal Title: 泌尿器外科 Volume: 23 Pages: 1079-1082
  • Peer Reviewed
• [Journal Article] Snail1 is stabilized byO-GlcNAc modification in hyperglycaemic condition (2010)
  • Author(s): Park SY, Kim HS, Konishi, N.
  • Journal Title: EMBO J Volume: 29 Pages: 3787-3796
  • Peer Reviewed
• [Journal Article] Variations in health-related quality of life in Japanese men who underwent iodine-125 permanent brachytherapy for localized prostate cancer (2010)
  • Author(s): Tanaka, N., Fujimoto, K., Asakawa, I., Hirayama, A., Yoneda, T., Yoshida, K., Hirao, Y., Hasegawa M., Konishi, N
  • Journal Title: Brachytherapy Volume: 9 Pages: 300-306
  • Peer Reviewed
• [Journal Article] Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma (2010)
  • Author(s): Shimada, K, Konishi, N., et al
  • Journal Title: Cancer Science Volume: 101 Pages: 155-160
  • NAID: 10027199949
  • Peer Reviewed
• [Presentation] 前立腺の良性腺管、前癌病変および癌に浸潤する炎症細胞の免疫組織化学的解析 (2012)
  • Author(s): 藤井智美、島田啓司、井筒千賀、田中宣道、藤本清秀、平尾和也、小西 登
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] 前立腺炎に関わる炎症細胞の免疫組織化学的解析 (2012)
  • Author(s): 藤井智美, 島田啓司, 中谷公彦, 小西 登
  • Organizer: 第101回病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 前立腺癌小線源治療後の排尿障害に対するα-1 ブロッカーの硬化-ナフトピジル・シロドシン対照試験 (2012)
  • Author(s): 田中宣道, 堀 俊太, 森澤洋介, 篠原雅岳, 喜馬啓介, 穴井 智, 鳥本一匡, 平山暁秀, 藤本清秀, 浅川勇雄, 長谷川正俊, 小西 登, 平尾佳彦
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-04-21
• [Presentation] 前立腺疾患の発生・進展における間質リモデリングの役割 (2012)
  • Author(s): 穴井 智、井上剛志、三宅牧人、池田朋博、松村善昭、田中宣道、平尾佳彦、島田啓司、小西 登、藤本清秀
  • Organizer: 第28回前立腺シンポジウム
  • Place of Presentation: 東京
• [Presentation] 年齢・体積別生検本数ノモグラムを用いた前立腺生検における至適生検本数の検討 (2012)
  • Author(s): 田中宣道、飯田孝太、大西健太、橋村正哉、辰巳佳弘、桑田真臣、穴井 智、松村善昭、山本雅司、 島田啓司、 小西 登、平尾佳彦、藤本清秀
  • Organizer: 第28回前立腺シンポジウム
  • Place of Presentation: 東京
• [Presentation] 前癌病変および癌に浸潤する炎症細胞の免疫組織化学的解析 (2012)
  • Author(s): 藤井智美、島田啓司、井筒千賀、田中宣道、藤本清秀、平尾和也、小西 登
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 前立腺癌小線源治療後の排尿障害に対するα-1ブロッカーの硬化-ナフトピジル・シロドシン対照試験 (2012)
  • Author(s): 田中宣道, 堀 俊太, 森澤洋介, 篠原雅岳, 喜馬啓介, 穴井 智, 鳥本一匡, 平山暁秀, 藤本清秀, 浅川勇雄, 長谷川正俊, 小西 登,平尾佳彦
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 横浜
• [Presentation] 植村天受、PTEN 遺伝子改変マウスを用いた酢酸クロルマジノンによる前立腺癌発癌抑制効果 (2011)
  • Author(s): 小池浩之, デベラスコ マルコ, 山本 豊, 畑中祐二, ワン イー, 島田啓司, 吉川和宏, 荒尾徳三, 西尾和人, 小西 登
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-04-23
• [Presentation] PTEN遺伝子改変マウスを用いた酢酸クロルマジノンによる前立腺癌発癌抑制効果 (2011)
  • Author(s): 小池浩之, 島田啓司, 小西登, 植村天受, 他
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-04-23
• [Presentation] CD138(Syndecan-1)を介した前立腺癌進展メカニズムの解析 (2011)
  • Author(s): 島田啓司、藤井智美、穴井智、藤本清秀、平尾佳彦、小西登
  • Organizer: 第27回前立腺シンポジウム
  • Place of Presentation: 東京コンファレンスセンター(東京都)
• [Presentation] 前立腺癌初期 staging における骨シンチの有用性 (2010)
  • Author(s): 田中宣道,大塚憲司, 富岡厚志,穴井 智,三宅牧人, 井上剛志, 池田朋博,松村善昭,山本雅司, 藤本清秀,平尾佳彦, 小西 登
  • Organizer: 第26回前立腺シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-12-12
• [Presentation] 放射線抵抗性前立腺癌に対する分子標的治療の試み (2010)
  • Author(s): 穴井 智,井上剛志, 池田朋博,三宅牧人, 千原良友, 田中宣道,藤本清秀,平尾佳彦,島田啓司,小西 登
  • Organizer: 第26回前立腺シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-12-11
• [Presentation] A novel signal associated with reactive oxygen species for maintenance of prostate cancer stem cell-like population (2010)
  • Author(s): Shimada, K., Anai, S., Fujimoto, K., Hirao, Y., Tasaki, M., Konishi, N
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer (2010)
  • Author(s): Koike, H., Marco A. De Velasco, Shimada, K., Yoshikawa, K., Arao, T., Nishio, K., Konishi, N., Uemura, H
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] The phosphorylation status of FADD in biopsy specimens is associated with biochemical recurrence after prostatectomy (2010)
  • Author(s): Marco A. De Velasco, Koike, H., Shimada, K., Yoshikawa, K., Konishi, N., Arao, T., Nishio, K., Uemura, H
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Gleason 分類とハイリスク前立腺癌 (2010)
  • Author(s): 小西 登, 島田啓司, 池田朋博, 田中宣道
  • Organizer: 第37回尿路悪性腫瘍研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-17
• [Presentation] CD138 を介したホルモン不応性前立腺癌進展メカニズムの解析と病理学的意義について (2010)
  • Author(s): 島田啓司,Marco A. De Velasco, 植村天受,田崎正人,小西 登
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-28
• [Presentation] 前立腺全摘標本における Molecular Profileによる再発予測 (2010)
  • Author(s): 穴井 智,井上剛志, 三宅牧人,池田朋博,富岡厚志,桑田真臣,松村善昭,谷 善啓,田中宣道,藤本清秀,平尾佳彦,島田啓司,小西 登
  • Organizer: 第98回日本泌尿器科学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-27
• [Book] 最新医学 第67巻/第3号 特集 がんの分子病理診断 -免疫染色と遺伝子診断の進歩- (2012)
  • Author(s): 小西 登、島田啓司
  • Publisher: 最新医学社
• [Book] 最新医学 第67巻/第3号 特集 がんの分子病理診断 -免疫染色と遺伝子診断の進歩- (2012)
  • Author(s): 小西 登、島田啓司
  • Publisher: 最新医学社
• [Book] 病理と臨床(第28巻、12章 男性生殖器、神経周囲浸潤) (2010)
  • Author(s): 小西登
  • Total Pages: 2
  • Publisher: 文光堂