Study of inflammation in prostate carcinogenesis

• Project/Area Number: 24592388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Osaka University
• Principal Investigator: NONOMURA Norio 大阪大学, 医学(系)研究科(研究院), 教授 (30263263)
• Co-Investigator(Kenkyū-buntansha): NAKAI Yasutomo 大阪大学, 医学系研究科, 講師 (20432479) ; TAKAYAMA Hitoshi 大阪大学, 医学系研究科, 講師 (50403051) ; FUJITA Kazutoshi 大阪大学, 医学系研究科, 助教 (50636181)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 前立腺 / 発癌 / 炎症 / 骨髄由来細胞 / 前立腺癌 / 幹細胞 / 再生

Outline of Final Research Achievements

Using chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats , we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide.
Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. We collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate. The number of cells in this population significantly increased in injured prostate compared with normal prostate tissue.In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow.

Research Products

• [Journal Article] Evaluation of PSF1 as a prognostic biomarker for prostate cancer. (2015)
  • Author(s): Tahara H, Naito H, Kise K, Wakabayashi T, Kamoi K, Okihara K, Yanagisawa A, Nakai Y, Nonomura N, Morii E, Miki T, Takakura N
  • Journal Title: Prostate Cancer Prostatic Dis Volume: 18 Issue: 1 Pages: 56-62
  • DOI: 10.1038/pcan.2014.46
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bone marrow-derived cells contribute to regeneration of injured prostate epithelium and stroma. (2015)
  • Author(s): Nakata W, Nakai Y, Yoshida T, Sato M, Hatano K, Nagahara A, Fujita K, Uemura M, Nonomura N.
  • Journal Title: Prostate Volume: in press Issue: 8 Pages: 806-814
  • DOI: 10.1002/pros.22962
  • Peer Reviewed
• [Journal Article] Serum fucosylated haptoglobin as a novel prognostic biomarker predicting high-Gleason prostate cancer. (2014)
  • Author(s): Fujita K, Shimomura M, Uemura M, Nakata W, Sato M, Nagahara A, Nakai Y, Takamatsu S, Miyoshi E, Nonomura N.
  • Journal Title: Prostate Volume: 74 Issue: 10 Pages: 1052-1058
  • DOI: 10.1002/pros.22824
  • Peer Reviewed
• [Journal Article] DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells. (2014)
  • Author(s): Fukuhara S, Chang I, Mitsui Y, Chiyomaru T, Yamamura S, Majid S, Saini S, Hirata H, Deng G, Gill A, Wong DK, Shiina H, Nonomura N, Dahiya R, Tanaka Y.
  • Journal Title: Oncotarget Volume: 5 Pages: 11297-11307
  • Peer Reviewed / Open Access
• [Journal Article] Inflammation and prostate carcinogenesis. (2013)
  • Author(s): Nakai, Y. and N. Nonomura
  • Journal Title: Int J Urol, Volume: 20 Issue: 2 Pages: 150-160
  • DOI: 10.1111/j.1442-2042.2012.03101.x
  • NAID: 10031146981
  • Peer Reviewed
• [Journal Article] White blood cell count is positively associated with benign prostatic hyperplasia. (2013)
  • Author(s): Fujita K, Hosomi M, Nakagawa M, Tanigawa G, Imamura R, Uemura M, Nakai Y, Takayama H, Yamaguchi S, Nonomura N:
  • Journal Title: Int J Urol. Volume: 21 Issue: 3 Pages: 308-312
  • DOI: 10.1111/iju.12243
  • Peer Reviewed
• [Journal Article] Residual Prostate Cancer Cells after Docetaxel Therapy Increase the Tumorigenic Potential via Constitutive Signaling of CXCR4, ERK1/2 and c-Myc (2013)
  • Author(s): Hatano K, Yamaguchi S, Nimura K, Murakami K, Nagahara A, Fujita K, Uemura M, Nakai Y, Tsuchiya M, Nakayama M, Nonomura N, *Kaneda Y.
  • Journal Title: Mol Cancer Research Volume: 11 Issue: 9 Pages: 1088-1100
  • DOI: 10.1158/1541-7786.mcr-13-0029-t
  • Peer Reviewed
• [Journal Article] Microvessel area of immature vessels is a prognostic factor in renal cell carcinoma. (2013)
  • Author(s): Sato M, Nakai Y, Nakata W, Yoshida T, Hatano K, Kawashima A, Fujita K, Uemura M, Takayama H, Nonomura N
  • Journal Title: Int J Urol. Volume: 21 Issue: 2 Pages: 130-134
  • DOI: 10.1111/iju.12231
  • Peer Reviewed
• [Journal Article] EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome. (2013)
  • Author(s): Sato M, Nakai Y, Nakata W, Yoshida T, Hatano K, Kawashima A, Fujita K, Uemura M, Takayama H, Nonomura N
  • Journal Title: PLoS One. Volume: 20 Issue: 9 Pages: e74313-e74313
  • DOI: 10.1371/journal.pone.0074313
  • Peer Reviewed
• [Presentation] 前立腺がん患者における血中フコシル化ハプトグロビンの解析および新規バイオマーカーとしての有用性の検討 (2015)
  • Author(s): 藤田和利、中田 渡、河嶋厚成、氏家 剛、永原 啓、植村元秀、下村真由香、中の三弥子、三善英知、野々村祝夫
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18 – 2015-04-21
• [Presentation] ミトコンドリアDNAに対する次世代シーケンスを用いた前立腺全摘標本および前立腺生検標本におけるクローン解析 (2015)
  • Author(s): 河嶋厚成、John Okello、氏家 剛、永原 啓、藤田和利、David Berman、野々村祝夫
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18 – 2015-04-21
• [Presentation] ドセタキセル抵抗性の前立腺癌細胞では、CXCR4・p-ERK1/2・c-Mycのsignaling loopが形成され、腫瘍造成能が亢進している (2015)
  • Author(s): 川村憲彦、波多野浩士、中田 渡、吉田栄宏、河嶋厚成、氏家 剛、永原 啓、藤田和利、植村元秀、金田安史、野々村祝夫
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18 – 2015-04-21
• [Presentation] Bone marrow-derived cells contribute to regeneration of Injured prostate epithelium and stroma (2014)
  • Author(s): Nakata W, Nakai Y, Yoshita T, Hatano K, Sato M, Nagahara A, Fujita K, Uemura M, Nonomura N.
  • Organizer: AUA Annual Meeting 2015
  • Place of Presentation: Orlando (USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Serum fucosylated haptoglobin as a novel prognostic biomarker predicting prostate cancer with Gleason 7 or more. (2014)
  • Author(s): Fujita K, Shimomura M, Nagahara A, Uemura M, Nakata W, Sato M, Nakai Y, Miyoshi E, Nonomura N.
  • Organizer: 29th Annual meeting of the European Association of Urology
  • Place of Presentation: Stockholm (Sweden)
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Serum fucosylated haptoglobin as a novel prognostic biomarker predicting prostate cancer: Detailed analysis of its oligosaccharide structures. (2014)
  • Author(s): Fujita K, Shimomura M, Nagahara A, Uemura M, Nakata W, Sato M, Nakai Y, Miyoshi E, Nonomura N.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] 膀胱内注入療法に用いられる高濃度の抗癌剤は膀胱癌細胞のミトコンドリア機能を阻害し寝黒－シスを誘導する (2014)
  • Author(s): 吉田栄宏、生山裕照、中山雅志、西村和郎、井上正宏、野々村祝夫
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形
• [Presentation] 前立腺の炎症－再生プロセスにおける骨髄由来細胞の役割 (2014)
  • Author(s): 中田 渡、中井康友、川村憲彦、吉田栄宏、佐藤元孝、永原 啓、藤田和利、植村元秀、野々村祝夫
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形
• [Presentation] 前立腺癌発癌と免疫細胞 (2013)
  • Author(s): 中井康友、藤田和利、野々村祝夫
  • Organizer: 第33回日本アンドロロジー学会
  • Place of Presentation: 大阪
• [Presentation] MYCによるリボゾーマルＲＮＡのエピジェネティクスおよび転写因子による発現制御 メカニズム (2013)
  • Author(s): 植村元秀、中田 渡、吉田 栄宏、佐藤 元孝、波多野浩士、中井 康友、高山 仁志、野々村 祝夫
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
• [Presentation] EMMPRINは腎細胞癌細胞の血管新生、増殖、浸潤を促進し、その予後規定因子となる (2013)
  • Author(s): 佐藤 元孝、中井 康友、中田 渡、吉田 栄宏、波多野 浩士、藤田 和利、植村 元秀、高山 仁志、野々村 祝夫
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
• [Presentation] EMMPRIN promotes angiongensis, proliferation and invasion of renal cell carcinoma (2013)
  • Author(s): Sato M, Nakai Y, Nakata W, Yoshida T, Hatano K, Fujita K, Uemura M, Takayama H, Nonomura N.
  • Organizer: 第72日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Immunoexpression Status and Prognostic Significance of mTOR Pathway Members in Upper Tract Urothelial Carcinoma. (2013)
  • Author(s): Fujita K, Munari E, Faraj S, Chaux A, Gonzalez-Roibon N, Hicks J, Meeker A, Nonomura N, Netto GJ.
  • Organizer: 108th Annual Meeting of the American Urological Association
  • Place of Presentation: San Diego (USA)