Laminin-like molecule is a potent therapeutic and diagnostic target for bladder cancer.

• Project/Area Number: 22591762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: The University of Tokyo
• Principal Investigator: KOSHIKAWA Naohiko 東京大学, 医科学研究所, 准教授 (70334282)
• Co-Investigator(Renkei-kenkyūsha): SHUIN Taro 高知大学, 医学部, 教授 (70128601) ; SHUO Takuya 東京大学, 医科学研究所, 特任研究員 (90399006)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 腫瘍マーカー / 膀胱がん / ラミニン / 診断 / 尿路がん / 尿 / 診断マーカー / 予後マーカー

Research Abstract

In this study we demonstrated for the first time that monomeric laminin gamma2 chain was detected in urines obtained from the patients with early stage of bladder carcinomas by a sandwich ELISA assay using a specific antibody to human monomeric laminin gamma2 chain(To be submitted). Furthermore urinary monomeric laminin gamma2 was expressed not only in invasive but also in surface carcinomas. The diagnostic value of monomeric laminin gamma2 was higher than that of other marker proteins (MTA, NMP-22) of bladder carcinoma urine. These results strongly suggest that urinary monomeric laminin gamma2 has the possibility to be a potent novel tumor marker for bladder carcinoma.

Research Products

• [Journal Article] Detection of the heterogeneous O-glycosylation profile of MT1-MMPexpressed in cancer cells by a simple MALDI-MS method. (2012)
  • Author(s): Shuo T, Koshikawa N, Hoshino D, Minegishi T, Ao-Kondo H, Oyama M, Sekiya S, Iwamoto S, Tanaka K, Seiki M.
  • Journal Title: PLoS One. Volume: 7(8) Issue: 8 Pages: e43751-e43751
  • DOI: 10.1371/journal.pone.0043751
  • Peer Reviewed
• [Journal Article] Control and inhibition analysis of complex formation processes. (2012)
  • Author(s): Saitou T, Itano K, Hoshino D, Koshikawa N, Seiki M, Ichikawa K, Suzuki T.
  • Journal Title: Theor Biol Med Model. Volume: 3 Issue: 1 Pages: 33-33
  • DOI: 10.1186/1742-4682-9-33
  • Peer Reviewed
• [Journal Article] MT1-MMP plays a critical role in henatopoiesis by regulating HIF-mediated chemo-/cytokine gene transcription within niche cells. (2012)
  • Author(s): Chiemi Nishida, Kaori Kusubata, Yoshihiko Tashiro, Ismael Gritli, Aki Sato, Makiko Ohki-Koizumi, Yohei Morita, Makoto Nagano, Takeharu Sakamoto, Naohiko Koshikawa, Takahiro Kuchimaru, Shinae Kizaka-Kondoh, Motoharu Seiki, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
  • Journal Title: Blood Volume: 119 Issue: 23 Pages: 5404-5416
  • DOI: 10.1182/blood-2011-11-390849
  • Peer Reviewed
• [Journal Article] Establishment and validation of computational model for MT1-MMP dependent ECM degradation and intervention strategies (2012)
  • Author(s): Hoshino, D., Koshikawa, N., Suzuki, T., Quaranta, V., Weaver, A.M., (Seiki, M.), Ichikawa, K.
  • Journal Title: PLoS Comp.Biol. Volume: 8 Issue: 4 Pages: e1002479-e1002479
  • DOI: 10.1371/journal.pcbi.1002479
  • Peer Reviewed
• [Journal Article] Turnover of focal adhesions and cancer cell migration. (2012)
  • Author(s): Nagano M, Hoshino D, Koshikawa N, Akizawa T, Seiki M.
  • Journal Title: Int J Cell Biol. Volume: 2012 Pages: 310616-310616
  • DOI: 10.1155/2012/310616
  • Peer Reviewed
• [Journal Article] Mathematical modeling of invadopodia formation (2012)
  • Author(s): T.Saitou, M.Rouzimaimaiti, N.Koshikawa, M.Seiki, K.Ichikawa, T.Suzuki
  • Journal Title: J.Theoretical Biology Volume: 298 Pages: 138-146
  • DOI: 10.1016/j.jtbi.2011.12.018
  • Peer Reviewed
• [Journal Article] Identification of proteins that associate with integrin α2 by proteomic analysis in human fibrosarcoma HT-1080 cells. (2012)
  • Author(s): Uematsu T, Konishi C, Hoshino D, HanX, Tomari T, Egawa N, Takada Y, IsobeT, Seiki M, Koshikawa N.
  • Journal Title: J Cell Physiol. Volume: 227(8) Issue: 8 Pages: 3072-9
  • DOI: 10.1002/jcp.23054
  • Peer Reviewed
• [Journal Article] Identification of proteins that associate with integrin α2 by proteomic analysis in human fibrosarcoma HT-1080 cells (2012)
  • Author(s): Uematsu T., et al.
  • Journal Title: J Cell Physiol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Expression of laminin 5-Y2 chain in cutaneous squamous cell carcinoma and its role in tumour invasion. (2011)
  • Author(s): Hamasaki H, Koga K, Aoki M, Hamasaki M, Koshikawa N, Seiki M, Iwasaki H, Nakayama J, Nabeshima K
  • Journal Title: Br J Cancer. Volume: 6;105(6) Issue: 6 Pages: 824-32
  • DOI: 10.1038/bjc.2011.283
  • Peer Reviewed
• [Journal Article] ZF21 protein, a regulator of the disassembly of focal adhesions and cancer metastasis, contains a novel noncanonical pleckstrin homology domain (2011)
  • Author(s): Nagano M, Hoshino D, Koshiba S, Shuo T Koshikawa N, Tomizawa T, Hayashi F, Tochio N, Harada T, Akizawa T Watanabe S, Handa N, Shirouzu M, Kigawa T, Yokoyama S, Seiki M
  • Journal Title: J Biol Chem. Volume: 286(36) Issue: 36 Pages: 31598-609
  • DOI: 10.1074/jbc.m110.199430
  • Peer Reviewed
• [Journal Article] Membrane-type 4 matrix metalloproteinase (MT4-MMP)modulates water homeostasis in mice. (2011)
  • Author(s): Srichai MB, Colleta H, Gewin L, Matrisian L, Abel TW, Koshikawa N, Seiki M, Pozzi A, Harris RC, Zent R.
  • Journal Title: PLoS One. Volume: 6(2) Issue: 2 Pages: e17099-e17099
  • DOI: 10.1371/journal.pone.0017099
  • Peer Reviewed
• [Journal Article] Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice (2011)
  • Author(s): Onozuka I, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 406 Issue: 1 Pages: 134-140
  • DOI: 10.1016/j.bbrc.2011.02.012
  • Peer Reviewed
• [Journal Article] A p27(kip1)-binding protein, p27RF-Rho, promotes cancer metastasis via activation of RhoA and RhoC. (2011)
  • Author(s): 12: Hoshino D, Koshikawa N, Seiki M.
  • Journal Title: J Biol Chem. Volume: 286(4) Issue: 4 Pages: 3139-48
  • DOI: 10.1074/jbc.m110.159715
• [Journal Article] Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells. (2011)
  • Author(s): 13: Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, Miyamoto S, Mekada E, Seiki M.
  • Journal Title: Cancer Sci. Volume: 102(1) Issue: 1 Pages: 111-6
  • DOI: 10.1111/j.1349-7006.2010.01748.x
  • NAID: 10029288679
• [Journal Article] ZF21 is a new regulator of focal adhesion disassembly and a potential member of the spreading initiation center. (2011)
  • Author(s): 14: Nagano M, Hoshino D, Sakamoto T, Akizawa T, Koshikawa N, Seiki M.
  • Journal Title: Cell Adh Migr. Volume: 5(1) Pages: 23-8
• [Journal Article] I Expression of laminin 5-γ2 chain in cutaneous squamous cell carcinoma and its role in tumour invasion (2011)
  • Author(s): Hamasaki H., et al.
  • Journal Title: Br J Cancer Volume: 105 Pages: 824-832
  • Peer Reviewed
• [Journal Article] Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinasel in ovarian carcinoma cells. (2011)
  • Author(s): Koshikawa, N., et al.
  • Journal Title: Cancer Science Volume: 102 Pages: 111-116
  • Peer Reviewed
• [Journal Article] A p27 (kip1)-binding protein, p27RF-Rho, promotes cancer metastasis via activation of RhoA and RhoC. (2011)
  • Author(s): Hoshino, D, Koshikawa, N., et al
  • Journal Title: J Biol.Chem. Volume: 286 Pages: 3139-3148
  • Peer Reviewed
• [Journal Article] MT1-MMP-mediated basement membrane remodeling modulates renal development. (2010)
  • Author(s): 15: Riggins KS, Mernaugh G, Su Y, Quaranta V, Koshikawa N, Seiki M, Pozzi A, Zent R.
  • Journal Title: Exp Cell Res. Volume: 316(17) Issue: 17 Pages: 2993-3005
  • DOI: 10.1016/j.yexcr.2010.08.003
• [Journal Article] Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into aheparin-independent growth factor. (2010)
  • Author(s): Koshikawa N, Mizushima H, Minegishi T, Iwamoto R, Mekada E, Seiki M.
  • Journal Title: Cancer Res. Volume: 70(14) Issue: 14 Pages: 6093-103
  • DOI: 10.1158/0008-5472.can-10-0346
• [Journal Article] ZF21 protein regulates cell adhesion and motility. (2010)
  • Author(s): Nagano M, Hoshino D, Sakamoto T, Kawasaki N, Koshikawa N, Seiki M.
  • Journal Title: J Biol Chem. Volume: 285(27) Issue: 27 Pages: 21013-22
  • DOI: 10.1074/jbc.m110.106443
• [Journal Article] Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor. (2010)
  • Author(s): Koshikawa, N, et al
  • Journal Title: Cancer Res. Volume: 70 Pages: 6093-6103
  • Peer Reviewed
• [Presentation] Membrane type-1 matrix metalloproteinase is a potent regulator of cancer malignant progression through the heparin-binding EGF-like growth factor activation. (2013)
  • Author(s): Koshikawa, N. et al.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2013-01-24
• [Presentation] Membrane type-1 matrix metalloproteinase (MT1-MMP) is a potent regulator of cancer malignant progression through the heparin-binding EGF-like growth factor activation (2013)
  • Author(s): Naohiko KOSHIKAWA
  • Organizer: AACR special conference "Invasion and Metastasis"
  • Place of Presentation: San Diego, CA USA
• [Presentation] 尿中腫瘍分泌蛋白 X 検出による尿路上皮癌診断の可能性 (2012)
  • Author(s): 鎌田雅行、越川直彦他
  • Organizer: 日本癌治療学会
  • Place of Presentation: 横浜
  • Year and Date: 2012-10-25
• [Presentation] 尿中腫瘍分泌蛋白X検出による尿路上皮癌診断の可能性 (2012)
  • Author(s): 鎌田雅行
  • Organizer: 日本癌治療学会
  • Place of Presentation: 横浜
• [Presentation] Proteolytic activation of HB-EGF by MT1-MMP inovarian carcinoma cells. (2011)
  • Author(s): Koshikawa, N. et al.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-07
• [Presentation] Proteolytic activation of HB-EGF by MT1-MMP in ovarian carcinoma cells (2011)
  • Author(s): 越川直彦, 他
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2011-10-07
• [Presentation] がん微小環境での悪性化制御因子としてのMT1-MMPの役割 (2011)
  • Author(s): 越川直彦
  • Organizer: 日本癌学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-09-24
• [Presentation] がん細胞膜上の微小環境-悪性化制御因子としてのMT1-MMP- (2011)
  • Author(s): 越川直彦, 他
  • Organizer: 第20回日本がん転移学会学術総会
  • Place of Presentation: 浜松(招待講演)
  • Year and Date: 2011-06-30
• [Presentation] MT1-MMP is a potent regulator of malignant progression in tumor microenvironment (2011)
  • Author(s): Koshikawa, N., Seiki, M
  • Organizer: Mathematical Methods in Cancer Cell Biology
  • Place of Presentation: Hiroshima, Japan(招待講演)
  • Year and Date: 2011-06-08
• [Presentation] がん細胞膜上の微小環境 (2011)
  • Author(s): 越川直彦他
  • Organizer: 第20回日本がん転移学会学術総会
  • Place of Presentation: 浜松
• [Presentation] MT1-MMP is a potent regulator of malignant progression in tumor microenvironment. (2011)
  • Author(s): Koshikawa, N. et al.
  • Organizer: 国際研究集会「がん細胞の数理科学」
  • Place of Presentation: 広島
• [Presentation] MT1-MMP is a potent regulator of malignant progression in tumor microenvironment (2010)
  • Author(s): 越川直彦
  • Organizer: 米国マトリックス生物学会 総会
  • Place of Presentation: 米国・チャールストン
  • Year and Date: 2010-10-26
• [Presentation] MT1-MMP is a potent regulator of malignant progression in tumor microenvironment. (2010)
  • Author(s): Koshikawa, N. et al.
  • Organizer: 米国マトリックス生物学会 10 周年記念総会
  • Place of Presentation: Charleston, USA
• [Presentation] がん微小環境での悪性化制御因子としてのMT1-MMPの役割 (2010)
  • Author(s): 越川直彦他
  • Organizer: 第69回 日本癌学会総会
  • Place of Presentation: 大阪
• [Remarks]
  • URL: http://www.motoharu-seiki.com
• [Remarks]
  • URL: http://www.motoharu-seiki.com/esults/