The roles of laminin alpha5 in tumor invasion

• Project/Area Number: 26430123
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: KIKKAWA YAMATO 東京薬科大学, 薬学部, 准教授 (20274227)
• Co-Investigator(Renkei-kenkyūsha): NOMIZU Motoyoshi 東京薬科大学, 薬学部, 教授 (00311522)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ラミニン / 基底膜 / 細胞外マトリックス / 癌 / 細胞接着 / 細胞運動 / ルテラン / インテグリン

Outline of Final Research Achievements

Epithelial cells stably anchor to basement membrane, whereas malignant tumors pass through it to achieve metastasis. Of basement membrane components, laminin-511 (alpha5, beta1, gamma1; LM-511) is a major isoform in many adult tissues. Several studies have shown that LM-511 promotes not only cell adhesion but also tumor cell migration. Thus, LM-511 can be viewed like two distinct molecules in normal vs. tumor cells. In this study, we focused on 1) the assembly of basement membrane containing LM-511 in tumor microenviroments and 2) the migration of tumor cells adhering to LM-511. The amino acid sequences active for endothelial cell tube formation were identified using synthetic peptides-derived from laminin alpha5 N-terminus. Our results also showed that endogenous LM-511 promotes the formation of cyst structure accompanying with basement membrane. Moreover, we found that the inside-out signal is involved in the transition from static to migratory cell behaviors on LM-511.

Research Products

• [Int'l Joint Research] Washington University in St.Louis(米国)
• [Int'l Joint Research] National Cancer Centre(シンガポール)
• [Journal Article] Identification of laminin α5 short arm peptides active for endothelial cell attachment and tube formation. (2017)
  • Author(s): Kikkawa, Y., Sugawara, Y., Harashima, N., Fujii, S., Ikari, K., Kumai, J., Katagiri, F., Hozumi, K., and Nomizu, M.
  • Journal Title: Journal of Peptide Science Volume: 印刷中 Issue: 7-8 Pages: 666-673
  • DOI: 10.1002/psc.2987
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An anti-human lutheran glycoprotein phage antibody inhibits cell migration on laminin-511: epitope mapping of the antibody. (2017)
  • Author(s): Enomoto-Okawa Y, Maeda Y, Harashima N, Sugawara Y, Katagiri F, Hozumi K, Hui KM, Nomizu M, Ito Y, Kikkawa Y
  • Journal Title: PLoS One Volume: 12 Issue: 1 Pages: e0167860-e0167860
  • DOI: 10.1371/journal.pone.0167860
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biological activity of peptide-conjugated polyion complex matrices consisting of alginate and chitosan. (2017)
  • Author(s): Fujimori, C‡., Kumai, J‡., Nakamura, K., Gu, Y., Hozumi, K., Katagiri, F., Kikkawa, Y., and Nomizu, M
  • Journal Title: Biopolymers Volume: 108 Issue: 1 Pages: 356-366
  • DOI: 10.1002/bip.22983
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Down-regulation of cell adhesion via rho-associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin-511 (2016)
  • Author(s): Kikkawa Y, Harashima N, Ikari K, Fujii S, Katagiri F, Hozumi K, Nomizu M
  • Journal Title: Exp Cell Res Volume: 344 Issue: 1 Pages: 76-85
  • DOI: 10.1016/j.yexcr.2016.04.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel hybrid compound of a plinabulin prodrug with an IgG binding peptide for generating a tumor selective noncovalent-type antibody-drug conjugate (2016)
  • Author(s): Muguruma K, Yakushiji F, Kawamata R, Akiyama D, Arima R, Shirasaka T, Kikkawa Y, Taguchi A, Takayama K, Fukuhara T, Watabe T, Ito Y, Hayashi Y
  • Journal Title: Bioconjug Chem Volume: 27 Issue: 7 Pages: 1606-1613
  • DOI: 10.1021/acs.bioconjchem.6b00149
  • Peer Reviewed / Open Access
• [Journal Article] Effect of spacer length and type on the biological activity of peptide-polysaccharide matrices. (2016)
  • Author(s): Kumai, J, Hozumi, K, Yamada, Y, Katagiri, F, Kikkawa, Y, Nomizu, M
  • Journal Title: Biopolymers Volume: 印刷中 Issue: 4 Pages: 512-520
  • DOI: 10.1002/bip.22785
  • Peer Reviewed / Open Access
• [Journal Article] Structural study of cell attachment peptide derived from laminin by molecular dynamics simulation. (2016)
  • Author(s): Yamada, H, Mori, S, Miyakawa, T, Morikawa, R, Katagiri, F, Hozumi, K, Kikkawa, Y, Nomizu, M, Takasu, M
  • Journal Title: PLoS One Volume: 11 Issue: 2 Pages: e0149474-e0149474
  • DOI: 10.1371/journal.pone.0149474
  • Peer Reviewed / Open Access
• [Journal Article] An efficacy of intensive vitamin D delivery to neointimal hyperplasia in recurrent vascular access stenosis. (2016)
  • Author(s): Sato, T, Iwasaki, Y, Kikkawa, Y, Fukagawa, M
  • Journal Title: J Vasc Access Volume: 17 Issue: 1 Pages: 72-77
  • DOI: 10.5301/jva.5000469
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices (2015)
  • Author(s): Kentaro Hozumi, Chikara Fujimori, Fumihiko Katagiri, Yamato Kikkawa, Motoyoshi Nomizu
  • Journal Title: Biomaterials Volume: 37 Pages: 73-81
  • DOI: 10.1016/j.biomaterials.2014.10.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] がん細胞の接着および運動における基底膜分子ラミニン-511とその受容体Lu/B-CAMの役割 (2015)
  • Author(s): 吉川大和
  • Journal Title: 生化学 Volume: 87 Pages: 609-611
  • NAID: 40020650196
  • Peer Reviewed / Open Access
• [Journal Article] Biological activities of the homologous loop regions in the laminin alpha chain LG modules. Biochemistry. (2014)
  • Author(s): Katagiri, F., Hara, T., Yamada, Y., Urushibata, S., Hozumi, K., Kikkawa, Y., Nomizu, M.
  • Journal Title: Biochemistry Volume: 53 Issue: 22 Pages: 3699-3708
  • DOI: 10.1021/bi5003822
  • Peer Reviewed
• [Journal Article] Screening of integrin-binding peptides in a laminin peptide library derived from the mouse laminin β chain short arm regions (2014)
  • Author(s): Katagiri F, Takagi M, Nakamura M, Tanaka Y, Hozumi K, Kikkawa Y, Nomizu M
  • Journal Title: Arch Biochem Biophys Volume: 550-551 Pages: 33-41
  • DOI: 10.1016/j.abb.2014.04.008
  • Peer Reviewed
• [Journal Article] Soluble lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro (2014)
  • Author(s): Kikkawa Y, Miwa T, Tanimizu N, Kadoya Y, Ogawa T, Katagiri F, Hozumi K, Nomizu M, Mizuguchi T, Hirata K, Mitaka T
  • Journal Title: Experimental Cell Research Volume: 328 Issue: 1 Pages: 197-206
  • DOI: 10.1016/j.yexcr.2014.07.012
  • Peer Reviewed / Open Access
• [Presentation] Identification of laminin alpha5 short arm peptides active for endothelial cell attachment and tube formation. (2016)
  • Author(s): Sugawara Y, Harashima N, Fujii S, Ikari K, Katagiri F, Hozumi K, Nomizu M, Kikkawa Y
  • Organizer: 2016 Annual Meeting the American Society for Cell Biology
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] The involvement of Lu/B-CAM spectrin binding motif in cell migration on LM-511. (2016)
  • Author(s): Harashima N, Sugawara Y, Ikari K, Katagiri F, Hozumi K, Nomizu M, Kikkawa Y
  • Organizer: 2016 Annual Meeting the American Society for Cell Biology
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Down-regulation of cell adhesion via rho-associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin-511. (2016)
  • Author(s): Kikkawa Y, Harashima N, Ikari K, Fujii S, Katagiri F, Hozumi K, Nomizu M
  • Organizer: American Society for Matrix Biology Biennial Meeting
  • Place of Presentation: St. Petersburg (USA)
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] 基底膜の機能解明からバイオマテリアルの創製へ (2016)
  • Author(s): 吉川大和、保住建太郎、片桐文彦、野水基義
  • Organizer: 第48回日本結合組織学会学術大会
  • Place of Presentation: 長崎大学、長崎市
  • Year and Date: 2016-06-24
• [Presentation] ROCK経路を介したラミニン-511に対する細胞接着の抑制と細胞運動の促進 (2016)
  • Author(s): 原島望、碇 和樹、藤井翔悟、片桐文彦、保住建太郎、野水基義、吉川大和
  • Organizer: 第48回日本結合組織学会学術大会
  • Place of Presentation: 長崎大学、長崎市
  • Year and Date: 2016-06-24
• [Presentation] 細胞-基質間における基底膜分子ラミニン-511とその受容体ルテランの役割 (2016)
  • Author(s): 吉川大和
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都テルサ、京都市
  • Year and Date: 2016-06-15
• [Presentation] Identification of active sequences in N-terminal region of laminin α5 involving endothelial cell attachment. (2015)
  • Author(s): Fujii, S., Harashima,N., Ikari, K., Katagiri, F., Hozumi, K., Nomizu, M., Kikkawa, Y
  • Organizer: 2015 Annual Meeting the American Society for Cell Biology
  • Place of Presentation: San Diego Convention Center, San Diego (USA)
  • Year and Date: 2015-12-12
• [Presentation] ラミニン-511上における癌細胞の運動促進メカニズム (2015)
  • Author(s): 原島望、藤井翔悟、碇和樹、片桐文彦、保住建太郎、野水基義、吉川大和
  • Organizer: 第三回MatriCellフォーラム
  • Place of Presentation: 三重大学、津
  • Year and Date: 2015-09-12
• [Presentation] Tumor cell migration on laminin-511 is promoted through the receptor binding reduced with PMA. (2015)
  • Author(s): Kikkawa, Y., Harashima,N., Ikari, K., Fujii, S., Katagiri, F., Hozumi, K., Nomizu, M
  • Organizer: 9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
  • Place of Presentation: Ewha Womans University, Seoul, Korea
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] ラミニン-511に対する細胞接着の抑制と細胞運動の促進 (2015)
  • Author(s): 藤井翔吾、碇和樹、片桐文彦、保住建太郎、野水基義、吉川大和
  • Organizer: 第47回日本結合組織学会学術大会
  • Place of Presentation: コクヨホール、東京
  • Year and Date: 2015-05-15
• [Presentation] An anti-human Lutheran phage antibody isolated from hepatocellular carcinoma phage library inhibits cell migration on laminin-511. (2014)
  • Author(s): Kikkawa, Y., Enomoto, Y., Ikari, K., Katagiri, F., Hozumi, K., Nomizu, M., and Ito, Y.
  • Organizer: The 2014 ascb/ifcb meeting
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia (USA)
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] Phorbol ester alters cell migration of lung adenocarcinoma on laminin-511. (2014)
  • Author(s): Ikari, K., Fujii, S., Katagiri, F., Hozumi, K., Nomizu, M., and Kikkawa, Y.
  • Organizer: The 2014 ascb/ifcb meeting
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia (USA)
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] Soluble Lutheran glycoprotein/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patiets and modulates cellular interaction with laminin-511 in vitro. (2014)
  • Author(s): Kikkawa, Y., Miwa, T., Tanimizu, N., Kadoya, Y., Ogawa, T., Katagiri, F., Hozumi, K., Nomizu, M., Mizuguchi, T., Hirata, K., and Mitaka, T.
  • Organizer: American Society for Matrix Biology Biennial Meeting 2014
  • Place of Presentation: Marriott Key center, Cleveland (USA)
  • Year and Date: 2014-10-12 – 2014-10-15
• [Presentation] 肝細胞癌由来scFvファージ抗体ライブラリを用いたルテラン特異的抗体の単離 (2014)
  • Author(s): 吉川 大和、榎元 友里恵、小川 貴穂、片桐 文彦、保住 建太郎、Hui Kam Man、野水 基義、伊東 祐二
  • Organizer: 第21回肝細胞研究会
  • Place of Presentation: 東京医科歯科大学、東京
  • Year and Date: 2014-06-27 – 2014-06-28
• [Presentation] ラミニンα５鎖受容体ルテラン（Lu/B-CAM）に対するファージ抗体の作製とその評価 (2014)
  • Author(s): 吉川 大和、榎本 友里恵、小川 貴穂、片桐 文彦、保住 建太郎、Hui Kam Man、野水 基義、伊東 祐二
  • Organizer: 第46回日本結合組織学会学術大会 第61回マトリックス研究会大会 合同学術集会
  • Place of Presentation: ウインク愛知、名古屋市
  • Year and Date: 2014-06-05 – 2014-06-07
• [Book] Encyclopedia of Signaling Molecules, 2nd Edition (2017)
  • Author(s): Kikkawa Y, Nishimune H
  • Total Pages: 11
  • Publisher: Springer
• [Remarks] 東京薬科大学 薬学部 病態生化学
  • URL: http://www.ps.toyaku.ac.jp/wp/byotaiseika/
• [Remarks] 吉川大和
  • URL: http://researchmap.jp/yamatokikkawa/
• [Remarks] 東京薬科大学 薬学部 病態生化学
  • URL: http://www.ps.toyaku.ac.jp/~nomizu/
• [Patent(Industrial Property Rights)] 抗癌剤 (2015)
  • Inventor(s): 吉川大和、福原武志、野水基義、伊東祐二
  • Industrial Property Rights Holder: 東京薬科大学、鹿児島大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-230926
  • Filing Date: 2015-11-26