Research of dynamic differentiation and morphogenesis in 3-D epithelial tubulogenesis

• Project/Area Number: 23790221
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Kanazawa University
• Principal Investigator: SAKAI Katsuya 金沢大学, がん進展制御研究所, 助教 (10523318)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 浸潤 / 再生医学 / 組織幹細胞 / がん化 / Tetraploid / 分化 / 形態形成

Research Abstract

We aimed to elucidate molecular mechanisms of epithelial cell invasiveness and differentiation underlying epithelial cell morphogenesis. Our results are as follows.
1) Mammary epithelial cell replication is not influenced by polyploidy.
2) Activation of MMP-2 by MT1-MMP is required for 3-D invasiveness. Cell surface localization of MT1-MMP was depend on 3-D. MMP-2 expression was strongly correlated to invasiveness and regulated by epigenetics. We identified epigenetic factors and these target genes possibly involved in cancer malignancy.
3) Cell surface Met was heterogeneously expressed in mammary epithelial cells and malignant melanomas. This might reflect invasive and malignant cell phenotypes.

Research Products

• [Journal Article] Met/HGF receptor activation is regulated by juxtamembrane Ser985 phosphorylation in hepatocytes (2013)
  • Author(s): Mizuho Nakayama
  • Journal Title: Cytokine Volume: XXX Issue: 3 Pages: 446-452
  • DOI: 10.1016/j.cyto.2013.04.006
  • Peer Reviewed
• [Journal Article] α-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells (2013)
  • Author(s): Michikoshi H, Nakamura T, Sakai K, (他4名)
  • Journal Title: Cancer Lett Volume: 335(2) Issue: 2 Pages: 472-478
  • DOI: 10.1016/j.canlet.2013.03.008
  • NAID: 120005254051
  • Peer Reviewed
• [Journal Article] Oral Administration of a Novel Long-acting Prostacyclin Agonist with Thromboxane Synthase Inhibitory Activity for Pulmonary Arterial Hypertension (2013)
  • Author(s): Atsuhiro Nakamura
  • Journal Title: Circulation journal Volume: XXX
  • Peer Reviewed
• [Journal Article] Suppression of acute hepatic injury by a synthetic prostacyclin agonist through hepatocyte growth factor expression (2012)
  • Author(s): Qing Xu
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. Volume: 302 Issue: 4 Pages: 420-429
  • DOI: 10.1152/ajpgi.00216.2011
  • Peer Reviewed
• [Journal Article] 3-D collagen-dependent cell surface expression of MT1-MMP and MMP-2 activation regardless of integrin β1 function and matrix stiffness (2011)
  • Author(s): Sakai K, Nakamura T, Suzuki Y, ImizuT, and Matsumoto K
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 1 Pages: 98-103
  • DOI: 10.1016/j.bbrc.2011.07.050
  • NAID: 120003308573
  • Peer Reviewed
• [Journal Article] Pleural mesothelioma instigates tumor associated fibroblasts to promote prog-ression via malignant cytokine network (2011)
  • Author(s): Li Q, Wang W, Yamada T, Matsumoto K, Bando Y, Uehara H, Nishioka Y, Sone S, Iwakiri S, Itoi K, Utsugi T, Yano S.
  • Journal Title: Am J Pathol Volume: 179 Issue: 3 Pages: 1483-93
  • DOI: 10.1016/j.ajpath.2011.05.060
  • Peer Reviewed
• [Journal Article] HGF-Antagonists: Structure, Activities, and Anti-cancer Approach (2011)
  • Author(s): Sakai K, Nakamura T, Kinoshita T, Nakamura T, Matsumoto K
  • Journal Title: Current Signal Transduction Therapy Volume: 6 Pages: 191-199
  • URL: http://dx.doi.org/10.2174/157436211795659964
  • Peer Reviewed
• [Journal Article] 3-D collagen-dependent cell surface expression of MT1-MMP and MMP-2 activation regardless of integrin β1 function and matrix stiffness (2011)
  • Author(s): Sakai K
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 412 Pages: 98-103
  • NAID: 120003308573
  • Peer Reviewed
• [Presentation] Dysfunction of polycomb group CBX protein is possibly involved in tumor malignancy (2013)
  • Author(s): Sakai K, Nakamura T, Suzuki Y, Suzuki T, Yano S, Takahashi C, and Matsumoto K
  • Organizer: 第3回新学術領域発がんスパイラル国際シンポジウム&金沢国際がん生物学シンポジウム
  • Place of Presentation: 金沢エクセルホテル東急(石川県)
• [Presentation] マウス乳腺上皮細胞における4倍体細胞の形成と増殖能の解析 (2012)
  • Author(s): 酒井 克也、松本 邦夫
  • Organizer: 第71回 日本癌学会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-21
• [Presentation] マウス乳腺上皮細胞における4倍体細胞の形成と増殖能の解析 (2012)
  • Author(s): 酒井 克也
  • Organizer: 日本癌学会
  • Place of Presentation: ロイトン札幌 (北海道)
• [Presentation] Aberrant Regulation of Epigenetic Silencing in 3-D Tumor Invasion (2012)
  • Author(s): Katsuya Sakai
  • Organizer: Japan - Korea Cancer Research Workshop
  • Place of Presentation: Westin Chosun Hotel (Busan, Korea)
• [Presentation] Aberrant Regulation of Epigenetic Silencing in 3-D Tumor Invasion (2011)
  • Author(s): Sakai K, Matsumoto K
  • Organizer: Japan - Korea Cancer Research Workshop
  • Place of Presentation: Westin Chosun Hotel (Korea)
• [Presentation] Epigenetic dysregulation of MMP-2 expression confers mesothelioma cell invasion (2011)
  • Author(s): Sakai K, Yano S, Matsumoto K
  • Organizer: 日本分子生物学会第11回春季シンポジウム&金沢国際がん生物学会シンポジウム
  • Place of Presentation: 石川県立音楽堂(石川県)
• [Book] InTech (2011)
  • Author(s): Sakai K, Nakamura T, Suzuki Y, Matsumoto K
  • Publisher: Significance, Mechanisms, and Progress of Anticancer Drugs Targeting HGF-Met
  • URL: http://www.intechopen.com/books/advances-in-cancer-therapy/significance-mechanisms-and-progress-ofanticancerdrugs-targeting-hgf-met
• [Remarks]
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoudoutaiseigyo/index.html