Disorder of cell adhesion system in tumor progression

• Project/Area Number: 23300351
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Yokohama City University
• Principal Investigator: MIYAZAKI KAORU 横浜市立大学, 付置研究所, その他 (70112068)
• Co-Investigator(Renkei-kenkyūsha): HIGASHI Shouichi 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (10275076)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: がん浸潤 / 細胞接着分子 / ラミニン332 / ラミニンγ2 / 上皮間葉変換（EMT） / CD44 / がん幹細胞 / 腫瘍血管 / 腫瘍-間質相互作用 / がん浸潤モデル / コラーゲンゲル / HGF / TGF-beta / ラミニン / 線維芽細胞 / EMT / TGF-β / 細胞接着 / 浮遊性増殖 / 浸潤モデル / 微小管 / コラーゲンマトリックス / がんの浸潤 / 浮遊増殖 / 腹水

Research Abstract

Non-invasive tumor cells are fixed on basement membranes (BMs) by stably binding to cell adhesion proteins such as laminin-332 (Lm332). However, they start to invade the BMs and then stroma during tumor progression. In this study, we investigated the mechanism of tumor invasion, mainly focusing on the interaction of tumor cells with cell adhesion proteins. Major results are as follows.
Laminin gamma2 (Lm-g2), a subunit of Lm332, is often overexpressed in invasive human cancers and hence regarded as a tumor invasion marker. We found that (1) Lm-g2 is induced in association with epithelial-mesenchymal transition of tumor cells, and (2) amino-terminal fragments of Lm-g2 directly interacts with the cancer stem cell marker CD44 in metastatic cancer cells, leading to the stimulation of their migration. These results suggest the cooperation of the two important tumor markers for cancer progression. We also found that Lm-g2 acts on vascular endothelial cells, increasing vascular permeability.

Research Products

• [Journal Article] Amino-terminal fragments of laminin gamma2 chain retract vascular endothelial cells and increase vascular permeability. (2014)
  • Author(s): Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 2 Pages: 168-175
  • DOI: 10.1111/cas.12323
  • Peer Reviewed / Open Access
• [Journal Article] Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5). (2014)
  • Author(s): Kamoshida, G., Ogawa, T., Oyanagi, J., Sato, H., Komiya, E., Higashi, S., Miyazaki, K., Tsuji, T.
  • Journal Title: Clin. Exp. Metastasis Volume: 31 Issue: 3 Pages: 285-291
  • DOI: 10.1007/s10585-013-9627-0
  • Peer Reviewed
• [Journal Article] Angiomodulin (AGM/IGFBP-rP1) is a molecular marker of vascular endothelial cells activated by VEGF in human breast cancers. (2014)
  • Author(s): Komiya, E, Sato, H., Ise, I., Watanabe, N., Higashi, H., Miyagi, Y., Miyazaki, K.
  • Journal Title: Cancer Med Volume: 印刷中 Issue: 3 Pages: 537-549
  • DOI: 10.1002/cam4.216
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of transforming growth factor-β signaling potentiates tumor cell invasion into collagen matrix induced by fibroblast-derived hepatocyte growth factor. (2014)
  • Author(s): Oyanagi, J., Kojima, N., Sato, H., Higashi, S., Kikuchi, K., Sakai, K., Matsumoto, K., Miyazaki, K.
  • Journal Title: Exp Cell Res. Volume: 印刷中 Issue: 2 Pages: 267-279
  • DOI: 10.1016/j.yexcr.2014.04.009
  • Peer Reviewed / Open Access
• [Journal Article] Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2) (2013)
  • Author(s): Higashi, S., Hirose, T., Takeuchi, T., Miyazaki, K.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 13 Pages: 9066-9076
  • DOI: 10.1074/jbc.m112.441758
  • Peer Reviewed
• [Journal Article] Elevated expression of angiomodulin (AGM/GFBP-rP1) in tumor stroma and its roles in fibroblast activation (2012)
  • Author(s): Eriko Komiya
  • Journal Title: Cancer Science Volume: 102 Issue: 4 Pages: 691-699
  • DOI: 10.1111/j.1349-7006.2012.02203.x
  • Peer Reviewed
• [Journal Article] Polymerized Laminin-332 Matrix Supports Rapid and Tight Adhesion of Keratinocytes, Suppressing Cell Migration (2012)
  • Author(s): Kariya, Y., Miyazaki, K., al
  • Journal Title: PLoSONE Volume: 7 Issue: 5 Pages: 95-107
  • DOI: 10.1371/journal.pone.0035546
  • Peer Reviewed
• [Journal Article] Membrane-Bound and Exosomal Metastasis-Associated C4.4A Promotes Migration by Associating with the α_6β_4 Integrin and MT1-MMP (2012)
  • Author(s): Ngora, H., Miyazaki, K., et al
  • Journal Title: Neoplasia Volume: 14 Issue: 2 Pages: 95-107
  • DOI: 10.1593/neo.111450
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition stimulates human cancer cells to extend microtubule-based invasive protrusions and suppresses cell growth in collagen gel (2012)
  • Author(s): Oyanagi, J., Ogawa, T., Sato, H., Higashi, S., Miyazaki, K
  • Journal Title: PLoS ONE Volume: 7(12)
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition stimulates human cancer cells to extend microtubule-based invasive protrusions and suppresses cell growth in collagen gel. (2012)
  • Author(s): Oyanagi, J.
  • Journal Title: PLoS ONE Volume: 7 Pages: 1-13
• [Journal Article] Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers (2011)
  • Author(s): Mori, T., Miyazaki, K., et al
  • Journal Title: Cancer Sci. Volume: 102 Issue: 5 Pages: 1095-1100
  • DOI: 10.1111/j.1349-7006.2011.01892.x
  • NAID: 10029293987
  • Peer Reviewed
• [Journal Article] Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of beta-amyloid precursor protein-derived inhibitor (2011)
  • Author(s): Hashimoto, H., Takeuchi, T., Komatsu, K., Miyazaki, K., Sato, M., Higashi, S
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 33236-33243
  • Peer Reviewed
• [Journal Article] Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of beta-amyloid precursor protein-derived inhibitor. (2011)
  • Author(s): Hashimoto, H.
  • Journal Title: J. Biol. Chem. Volume: 206 Pages: 33236-33243
  • Peer Reviewed
• [Journal Article] Pericellular proteolysis by matrix metallo proteinase-7 is differentially modulated by cholesterol sulfate, sulfatide and cardiolipin
  • Author(s): Yamamoto, K., Miyazaki, K., Higashi, S
  • Journal Title: FEBS J Volume: (in press)
  • Peer Reviewed
• [Presentation] 基底膜分子ラドシン/ラミニン5/ラミニン332の構造と機能 (2013)
  • Author(s): 宮崎香
  • Organizer: 水疱症研究会
  • Place of Presentation: 大分, 藤原作平会頭
  • Year and Date: 2013-10-20
• [Presentation] Angiomodulin (AGM/IGFBP-rP1) is overexpressed in tumor vasculature and regulates adhesion of vascular endothelial cells via integrin αvβ3 : Possible roles in tumor angiogenesis (2013)
  • Author(s): Kaoru Miyazaki, Eriko Komiya, Hiroki Sato, Yohei Miyagi, Shouichi Higashi
  • Organizer: AACR Conference "Tumor Invasion and Metastasis"
  • Place of Presentation: San Diego, USA
• [Presentation] Laminin gannma2 Chain Induces Vascular Hyperpermeability through Its Heparin-Binding Site of N-terminal EGF-like Repeat (2013)
  • Author(s): Hiroki Sato, Shouichi Higashi and Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] A synthetic inhibitor of TGF- stimulates tumor cell invasion by enhancing secretion of HGF from fibroblasts in vitro (2013)
  • Author(s): Jun Oyanagi, Shouichi Higashi, Keiji Kikuchi, Katsuya Sakai, Kunio Matusmoto, Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Angiomodulin, a cancer blood vessel marker induced by VEGF, enhances vascular permeability through integrin alpha-v/beta-3 (2013)
  • Author(s): Eriko Komiya, Hiroki Sato, Shouich Higashi, Yohei Miyagi, Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ラミニンγ2鎖N末端領域に存在するヘパリン結合部位の血管透過性亢進活性 (2013)
  • Author(s): 佐藤拓輝, 宮崎香
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: 松本
• [Presentation] 細胞外マトリックスタンパク質ラミニン-332 による単球の分化とマトリックスメタロプロテイナーゼ-9 産生調節 (2013)
  • Author(s): 鴨志田 剛, 佐藤 拓輝, 宮崎 香, 辻 勉
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: 松本
• [Presentation] 基底膜分子ラドシン/ラミニン5/ラミニン332の構造と機能。 (2013)
  • Author(s): 宮崎香
  • Organizer: 水疱症研究会特別講演
  • Place of Presentation: 大分
  • Invited
• [Presentation] Laminin gannma2 Chain Induces Vascular Hyperpermeability through Its Heparin-Binding Site of N-terminal EGF-like Repeat. (2013)
  • Author(s): Hiroki Sato, Shouichi Higashi and Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] A synthetic inhibitor of TGF- stimulates tumor cell invasion by enhancing secretion of HGF from fibroblasts in vitro. (2013)
  • Author(s): Jun Oyanagi1, Shouichi Higashi, Keiji Kikuchi, Katsuya Sakai, Kunio Matsumoto, and Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Angiomodulin, a cancer blood vessel marker induced by VEGF, enhances vascular permeability through integrin alpha-v/beta-3. (2013)
  • Author(s): Eriko Komiya, Hiroki Sato, Shouich Higashi, Yohei Miyagi, Kaoru Miyazaki
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ラミニンγ2鎖N末端領域に存在するヘパリン結合部位の血管透過性亢進活性。 (2013)
  • Author(s): 佐藤拓輝、宮崎香
  • Organizer: 第22回日本がん転移学会
  • Place of Presentation: 松本
• [Presentation] 細胞外マトリックスタンパク質ラミニン-332 による単球の分化とマトリックスメタロプロテイナーゼ-9 産生調節。 (2013)
  • Author(s): 鴨志田剛 ,佐藤拓輝,宮崎香, 辻勉
  • Organizer: 第22回日本がん転移学会
  • Place of Presentation: 松本
• [Presentation] Angiomodulin (AGM/IGFBP-rP1) is overexpressed in tumor vasculature and regulates adhesion of vascular endothelial cells via integrinαvβ3: Possible roles in tumor angiogenesis. (2013)
  • Author(s): Kaoru Miyazaki
  • Organizer: AACR Conference
  • Place of Presentation: San Diego, USA
• [Presentation] Overxpression of Angiomodulin (AGM/IGFBPrP1) in Tumor Stroma and Vasculature : Differential Regulation and Functions (2012)
  • Author(s): Eriko komiya, Hiroki Sato, Yohei Miyagi, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: The 14th International Biennial Congress of the Metastasis Research Association
  • Place of Presentation: Brisbane, Australia
• [Presentation] Laminin γ2 chain Promotes Invasion of Tumor Cells into Vascular Endothelial Cell Layer In Vitro (2012)
  • Author(s): Hiroki Sato, Takashi Ogawa, Eriko Komiya, Jun Oyanagi, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: The 14th International Biennial Congress of the Metastasis Research Association
  • Place of Presentation: Brisbane, Australia
• [Presentation] Overxpression of Angiomodulin (AGM/IGFBPrP1) in Tumor Stroma and Vasculature : Differential Regulation and Functions (2012)
  • Author(s): Eriko Komiya, Hiroki Sato, Shouich Higashi, Yohei Miyagi, Kaoru Miyazaki
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] EMT of tumor cells promotes microtubule-based protrusions in 3D collagen matrix, suppressing cell growth (2012)
  • Author(s): Jun Oyanagi, Hiroki Sato, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Laminin γ2 Chain Induces Transendothelial Migration of Cancer Cells by Modulating Cytoskeleton of Endothelial Cells (2012)
  • Author(s): Hiroki Sato, Jun Oyanagi, Eriko Komiya, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Overexpression of Angiomodulin (AGM/IGFBP-rP1) in Tumor Stroma and Vasculature:Differential Regulation and Functions. (2012)
  • Author(s): Eriko Komiya
  • Organizer: The 14th International Biennial Congress of the Metastasis Research Association
  • Place of Presentation: Brisbane, Australia
• [Presentation] Laminin γ2 chain Promotes Invasion of Tumor Cells into Vascular Endothelial Cell Layer In Vitro. (2012)
  • Author(s): Hiroki Sato
  • Organizer: The 14th International Biennial Congress of the Metastasis Research Association.
  • Place of Presentation: Brisbane, Australia
• [Presentation] Overexpression of Angiomodulin (AGM/IGFBP-rP1) in Tumor Stroma and Vasculature: Differential Regulation and Functions. (2012)
  • Author(s): Eriko Komiya
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] EMT of tumor cells promotes microtubule-based protrusions in 3D collagen matrix, suppressing cell growth. (2012)
  • Author(s): Jun Oyanagi
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Laminin γ2 Chain Induces Transendothelial Migration of Cancer Cells by Modulating Cytoskeleton of Endothelial Cells. (2012)
  • Author(s): Hiroki Sato
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Epithelial-mesenchymal transition (EMT) stimulates tumor cells to produce invadopodia-like protrusions in collagen matrix, suppressing cell growth (2011)
  • Author(s): Jun Oyanagi, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: American Association for Cancer Research 102nd Annual Meeting Innovation and Collaboration to Progress
  • Place of Presentation: Florida in U.S.A
• [Presentation] ヒトがん細胞における細胞接着能消失メカニズムの解析 (2011)
  • Author(s): 関根玲子, 佐藤拓輝, 宮崎香
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
• [Presentation] ヒト間葉系幹細胞の増殖と分化に及ぼす各種ラミニン分子の作用 (2011)
  • Author(s): 藤田幸, 柳川聡秀, 今林司, 高橋瑛美, 小柳潤, 宮崎香
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
• [Presentation] APP 由来インヒビターペプチドによる MMP-2 選択的阻害機構の解明 (2011)
  • Author(s): 竹内友香, 橋本博, 宮崎香, 佐藤衛, 東昌市
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
• [Presentation] Epithelial-mesenchymal transition promotes invadopodia-like protrusions in collagen gel., suppressing cell growth (2011)
  • Author(s): Jun oyanagi, Hiroki Sato, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] TRPM5 is a transducer of extrscellular acidic pH in melanoma cells and contributes lung metastasis (2011)
  • Author(s): Yasumasa Kato, Ryuichiro Hata, Mamoru Tsukuda, Kaoru Miyazaki, Yoji Nagashima
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Tumor-derived adhesion factor IGFBP-rP1/TAF promotes growth of human fibroblasta and their fibronectin expression (2011)
  • Author(s): Eriko Komiya, Kaoru Miyazaki, Shouichi Higashi
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Laminin γ2 chain Promotes Invasion of Tumor Cells into Vascular Endothelial Cell Layer In Vitro (2011)
  • Author(s): Hiroki Sato, Jun Oyanagi, Shouichi Higashi, Kaoru Miyazaki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 血管基底膜に存在する新規ラミニン分子ラミニン 3B11 の発現と性質 (2011)
  • Author(s): 宮崎香
  • Organizer: 第43回日本結合組織学会
  • Place of Presentation: 別府
• [Presentation] がん浸潤マーカー・ラミニンγ2 鎖の血管内皮浸潤促進活性とその機構 (2011)
  • Author(s): 佐藤拓輝, 宮崎香
  • Organizer: 第20回日本がん転移学会学術集会・総会
  • Place of Presentation: 浜松
• [Presentation] Biomarkers in keratinocyte senescence and skin elasticity (2011)
  • Author(s): Chie Yasuda, Nakaba Kayanuma, Minako Takahashi, Shioji Ishiwatari, Kaoru Miyazaki, Shoko Matsukuma
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] Epithelial-mesenchymal transition (EMT) stimulates tumor cells to produce invadopodia-like protrusions in collagen matrix, suppressing cell growth. (2011)
  • Author(s): Jun Oyanagi
  • Organizer: American Association for Cancer Research 102nd Annual Meeting Innovation and Collaboration to Progress
  • Place of Presentation: Florida in U.S.A.
• [Presentation] ヒト間葉景観細胞の増殖と文化に及ぼす各種ラミニン分子の作用 (2011)
  • Author(s): 藤田幸
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
• [Presentation] APP由来インヒビターペプチドによるMMP-2選択的阻害機構の解明 (2011)
  • Author(s): 竹内友香
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
• [Presentation] Epithelial-mesenchymal transition promotes invadopodia-like protrusions in collagen gel, suppressing cell growth. (2011)
  • Author(s): Jun Oyanagi
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] TRPM5 is a transducer of extrscellular acidic pH in melanoma cells and contributes lung metastasis. (2011)
  • Author(s): Yasumasa Kato
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Tumor-derived adhesion factor IGFBP-rP1/TAF promotes growth of human fibroblasta and their fibronectin expression. (2011)
  • Author(s): Eriko Komiya
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Laminin γ2 chain Promotes Invasion of Tumor Cells into Vascular Endothelial Cell Layer In Vitro. (2011)
  • Author(s): Hiroki Sato
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 血管基底膜に存在する新規ラミニン分子ラミニン3B11の発現と性質 (2011)
  • Author(s): 宮崎香
  • Organizer: 日本結合組織学会会
  • Place of Presentation: 大分県別府
• [Presentation] がん浸潤マーカー・ラミニンγ2鎖の血管内皮浸潤促進活性とその機構 (2011)
  • Author(s): 佐藤拓輝
  • Organizer: 第20回日本がん転移学会学術集会・総会
  • Place of Presentation: 静岡県浜松
• [Presentation] Biomarkers in keratinocyte senescence and skin elasticity. (2011)
  • Author(s): Chie Yasuda
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Book] 「タンパク質実験ノート改訂第 4 版」(上巻) (2011)
  • Author(s): 岡田雅人, 宮崎香 編著
  • Total Pages: 215
  • Publisher: 羊土社
• [Book] 「タンパク質実験ノート改訂第 4 版」(下巻) (2011)
  • Author(s): 岡田雅人, 三木裕明, 宮崎香 編著
  • Total Pages: 222
  • Publisher: 羊土社
• [Book] 「タンパク質実験ノート改訂第4版」（上巻） (2011)
  • Author(s): 岡田雅人
  • Total Pages: 215
  • Publisher: 羊土社
• [Book] 「タンパク質実験ノート改訂第4版」（下巻） (2011)
  • Author(s): 岡田雅人
  • Total Pages: 222
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] ラミニン 5 を利用した間葉系幹細胞の培養技術 (2012)
  • Inventor(s): 宮崎香, 橋本じゅん子, 苅谷慶喜
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2012-05-25
• [Patent(Industrial Property Rights)] ラミニン 6B(ラミニン 3B11)蛋白質 (2012)
  • Inventor(s): 宮崎香
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2012-11-30
• [Patent(Industrial Property Rights)] ラミニン 5B (2011)
  • Inventor(s): 宮崎香, 苅谷慶喜
  • Industrial Property Rights Holder: 横浜 TLO
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2011-08-12
• [Patent(Industrial Property Rights)] Skin aging marker and technique for use thereof. US 特許認定 (2011)
  • Inventor(s): Satoshi Miyata, Kaoru Miyazaki, Chie Yasuda, Akihiro Iwamatsu
  • Industrial Property Rights Holder: 株式会社ファンケル
  • Industrial Property Rights Type: 特許
  • Acquisition Date: 2011-07-05
  • Overseas