A role of sialic acid for tumor angiogenesis

• Project/Area Number: 25430122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kitazume Shinobu 国立研究開発法人理化学研究所, 疾患糖鎖研究チーム, 副チームリーダー (80301753)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 血管内皮細胞 / 細胞接着 / PECAM / シアル酸 / レクチン / アポトーシス / 腫瘍血管新生 / ＰＥＣＡＭ / 腫瘍内血管新生 / α2,6-シアル酸 / 血管新生 / VEGF

Outline of Final Research Achievements

We expected that platelet endothelial cell adhesion molecule (PECAM) would possess lectin-like activity toward α2,6-sialic acid to ensure its homophilic interaction. We found that a longer α2,6-sialylated oligosaccharide exhibited strong inhibitory activity against homophilic PECAM interaction in vitro. Furthermore, we found that a cluster-type α2,6-sialyl N-glycan probe specifically bound to PECAM-immobilized beads. Moreover, addition of the α2,6-sialylated oligosaccharide to endothelial cells enhanced the internalization of PECAM as well as the sensitivity to apoptotic stimuli. Collectively, these findings suggest that PECAM is a sialic acid-binding lectin and that this binding property supports endothelial cell survival. Notably, our findings that α2,6-sialylated glycans influenced the susceptibility to endothelial cell apoptosis shed light on the possibility of using a glycan-based method to modulate angiogenesis.

Research Products

• [Journal Article] Glyco-redox, a link between oxidative stress and changes of glycans: Lessons from research on glutathione, reactive oxygen and nitrogen species to glycobiology. (2016)
  • Author(s): N. Taniguchi, Y. Kizuka, S. Takamatsu, E. Miyoshi, C. Gao, K. Suzuki, S. Kitazume, K. Ohtsubo
  • Journal Title: Arch. Biochem. Biphys. Volume: 595 Pages: 72-80
  • DOI: 10.1016/j.abb.2015.11.024
  • Peer Reviewed / Open Access
• [Journal Article] Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin (2016)
  • Author(s): A. Ogura, T. Tahara, S. Nozaki, K. Morimoto, Y. Kizuka, S. Kitazume, M. Hara, S. Kojima, H. Onoe, A. Kurbangalieva, N. Taniguchi, Y. Watanabe, K. Tanaka
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 21797-21797
  • DOI: 10.1038/srep21797
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions (2016)
  • Author(s): Kizuka Y, Nakano M, Kitazume S, Saito T, Saido TC, Taniguchi N
  • Journal Title: Biochemical Journal Volume: 473 Issue: 1 Pages: 21-30
  • DOI: 10.1042/bj20150607
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer’s disease (2015)
  • Author(s): Yasuhiko Kizuka, Shinobu Kitazume, Reiko Fujinawa, Takashi Saito, Nobuhisa Iwata, Takaomi C. Saido, Miyako Nakano, Yoshiki Yamaguchi, Yasuhiro Hashimoto
  • Journal Title: EMBO Mol. Med. Volume: 7(2) Issue: 2 Pages: 175-89
  • DOI: 10.15252/emmm.201404438
  • NAID: 120006799362
  • Peer Reviewed / Open Access
• [Journal Article] Clec4g (LSECtin) interacts with BACE1 and suppresses Aβ generation (2015)
  • Author(s): Kizuka Y, Kitazume S, Sato K, Taniguchi N
  • Journal Title: FEBS Letters Volume: 589 Issue: 13 Pages: 1418-1422
  • DOI: 10.1016/j.febslet.2015.04.060
  • Peer Reviewed / Open Access
• [Journal Article] Cell surface and in vivo interaction of dendrimeric N-glycoclusters. (2015)
  • Author(s): M. Taichi, S. Kitazume, K. Vong, R. Imamaki, A. Kurbangalieva, N. Taniguchi, and K. Tanaka
  • Journal Title: Glycoconjugate J. Volume: 32 Issue: 7 Pages: 497-503
  • DOI: 10.1007/s10719-015-9594-6
  • Peer Reviewed / Open Access
• [Journal Article] Interaction of platelet endothelial cell adhesion molecule (PECAM) with α2,6-sialylated glycan regulates its cell surface residency and anti-apoptotic role (2014)
  • Author(s): Kitazume, S., Imamaki, R., Kurimoto, A., Ogawa, K., Kato, M., Yamaguchi, Y., Tanaka, K., Ishida, H., Ando, H., Kiso, M., Hashii, N., Kawasaki, N. and Taniguchi, N.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 40 Pages: 27604-27613
  • DOI: 10.1074/jbc.m114.563585
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sweet role of platelet endothelial cell adhesion moleculr (PECAM) in understanding angiogenesis. (2014)
  • Author(s): S. Kitazume*, R. Imamaki, K. Ogawa, and N. Taniguchi
  • Journal Title: Glycobiology Volume: 24 Issue: 12 Pages: 1260-1264
  • DOI: 10.1093/glycob/cwu094
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A cascading reaction sequence involving ligand-directed azaelectrocyclization and autooxidation-induced fluorescence recovery enables visualization of target proteins on the surfaces of live cells. (2014)
  • Author(s): Tanaka, K., Kitadani, M., Tsutsui, A., Pradipta, AR., Imamaki, R., Kitazume, S., Taniguchi, N., Fukase K.
  • Journal Title: Org Biomol Chem. Volume: 12 Issue: 9 Pages: 1412-1418
  • DOI: 10.1039/c3ob42267d
  • Peer Reviewed
• [Journal Article] Soluble amyloid precursor protein 770 is a novel biomarker candidate for acute coronary syndrome (2013)
  • Author(s): Kitazume S, Yoshihisa A, Yamaki T, Oikawaa M, Tachida Y, Ogawa K, Imamaki R, Takeishi Y, Yamamoto N, Taniguchi N
  • Journal Title: Proteomics Clinical Applications Volume: 7 Issue: 9-10 Pages: 657-663
  • DOI: 10.1002/prca.201200135
  • Peer Reviewed
• [Journal Article] Mass isotopomer analysis of metabolically labeled nucleotide sugars and N-and o-glycans for tracing nucleotide sugar metabolisms (2013)
  • Author(s): Nakajima K, Ito E, Ohtsubo K, Shirato K, Takamiya R, Kitazume S, Angata T, Taniguchi N
  • Journal Title: Mol. Cell Proteomics Volume: 12(9) Issue: 9 Pages: 2468-2480
  • DOI: 10.1074/mcp.m112.027151
  • Peer Reviewed
• [Journal Article] Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination (2013)
  • Author(s): Kanekiyo K, Inamori K, Kitazume S, Sato K, Maeda J, Higuchi M, Kizuka Y, Korekane H, Matsuo I, Honke K, Taniguchi N
  • Journal Title: J. Neurosci. Volume: 33(24) Issue: 24 Pages: 10037-10047
  • DOI: 10.1523/jneurosci.3137-12.2013
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a Regulator of N-Acetylglucosaminyltransferase GnT-IX (GnT-Vb) (2013)
  • Author(s): Korekane H, Park JY, Matsumoto A, Nakajima K, Takamatsu S, Ohtsubo K, Miyamoto Y, Hanashima S, Kanekiyo K, Kitazume S, Yamaguchi Y, Matsuo I, Taniguchi N
  • Journal Title: J. Biol. Chem. Volume: 288(39) Issue: 39 Pages: 27912-27926
  • DOI: 10.1074/jbc.m113.474304
  • Peer Reviewed
• [Presentation] Interaction of PECAM with α,2,6-sialylated glycan regulates its cell surface residency and anti-apoptotic role (2014)
  • Author(s): 1.S. Kitazume
  • Organizer: RIKEN-Max Planck Joint Research Center for Systems Chemical Biology (3rd Annual Symposium)
  • Place of Presentation: Kreuth, Germany
  • Year and Date: 2014-05-23
  • Invited
• [Presentation] Solubule smyloid precrsor protein 770 is secreted in a O-glycosylated form from inflamed endothelial cells
  • Author(s): Shinobu Kitazume, Akiomi Yoshihisa, Takayoshi Yamaki, Masayoshi Oikawa, Yuriko Tachida, Kazuko Ogawa, Rie Imamaki, Yoshiaki Hagiwara, Noriaki Kinoshita, Yasuchika Takeishi, Nobuhisa Iwata, Takaomi Saido, Naomasa Yamamoto and Naoyuki Taniguchi
  • Organizer: Glyco22
  • Place of Presentation: 中国・大連
  • Invited
• [Presentation] 脱髄疾患の進行に関わる脳特異的な分岐型O-Man 糖鎖
  • Author(s): 兼清健志、稲森 啓一郎、○北爪しのぶ、前田純、樋口真人、是金宏昭、松尾一郎、本家孝一、谷口直之
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
  • Invited
• [Book] ST6Gal-I. Handbook of Glycosyltransferases and Related Genes. 2nd Edition. (2014)
  • Author(s): 1.S. Kitazume
  • Total Pages: 4
  • Publisher: Springer
• [Remarks] 脱髄(だつずい)を進行させる糖鎖を発見
  • URL: http://www.riken.jp/pr/press/2013/20130731_1/