Physiological significance of concerted action of cell adhesion molecules induced by hypoxia inducible factor

• Project/Area Number: 21590324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Aichi Medical University (2010-2011); Aichi Cancer Center Research Institute (2009)
• Principal Investigator: KANNAGI Reiji 愛知医科大学, 客員教授 (80161389)
• Co-Investigator(Renkei-kenkyūsha): SAKUMA Keiichiro 愛知県がんセンター(研究所), 分子病態学部, 主任研究員 (90402891) ; GOTO Yoshiko 愛知県がんセンター(研究所), 分子病態学部, 主任技師 (30416169)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 生体分子医学 / 低酸素誘導因子 / 低酸素 / CD44 / ヒアルロン酸 / セレクチン / 生理活性脂質 / 糖脂質 / セラミド / LPA / シアリルルイスX / ケモカイン / シンデカン / CCR7 / CXCR4 / ヘパラン硫酸 / ジヒドロセラミド / DES1遺伝子 / 質量分析(ESI-MS / MS) / 長鎖脂肪酸(VLCFA) / 不飽和脂肪酸

Research Abstract

We have explored what kind of changes in cell adhesion molecules are induced by cellular hypoxia, and have analyzed their cooperative interactions in cellular response to hypoxia. The results indicated that cellular hypoxia induces significant changes in both the glycan-and core lipid moieties within the glycolipid molecules simultaneously. The results indicated that hypoxia also induces simultaneous changes in both the glycan side chains and core protein moieties within the glycoprotein molecules. Our results suggested that these multiple changes appropriately cooperate in the physiological cellular response to cope with hypoxic environments in a synergistic manner.

Research Products

• [Journal Article] Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors, siglec-7 and-9 (2012)
  • Author(s): Miyazaki, K., Sakuma, K., Kawamura, Y. I., Izawa, M., Ohmori, K., Mitsuki, M., Yamaji, T., Hashimoto, Y., Suzuki, A., Saito, Y., Dohi, T., and Kannagi, R.
  • Journal Title: J. Immunol Volume: 188 Issue: 9 Pages: 4690-4700
  • DOI: 10.4049/jimmunol.1100605
  • Peer Reviewed
• [Journal Article] Quantitative transcriptomic profiling of branching in a glycosphingolipid biosynthetic pathway (2011)
  • Author(s): Takematsu H, Yamamoto H, Naito-Matsui Y, Fujinawa R, Tanaka K, Okuno Y, Tanaka Y, Kyogashima M, Kannagi R, Kozutsumi Y
  • Journal Title: J Biol Chem Volume: 286(31) Issue: 31 Pages: 27214-27224
  • DOI: 10.1074/jbc.m111.234526
  • Peer Reviewed
• [Journal Article] Sialylated and sulfated carbohydrate ligands for selectins and siglecs : involvement in traffic and homing of human memory T and B lymphocytes (2011)
  • Author(s): Kannagi, R., Ohmori, K., Chen, G. Y., Miyazaki, K., Izawa, M., and Sakuma, K.
  • Journal Title: Adv. Exp. Med. Biol Volume: 705 Pages: 549-569
  • DOI: 10.1007/978-1-4419-7877-6_29
  • ISBN: 9781441978769, 9781441978776
  • Peer Reviewed
• [Journal Article] TNFα enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl-and sulfotransferase genes involved in the synthesis of selectin ligands (2011)
  • Author(s): Radhakrishnan, P., Chachadi, V., Lin, M. F., Singh, R., Varki, A., Kannagi, R., and Cheng, P. W.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 409 Issue: 3 Pages: 436-441
  • DOI: 10.1016/j.bbrc.2011.05.019
  • Peer Reviewed
• [Journal Article] Systematic analyses of free ceramide species and ceramide species comprising neutral glycosphingolipids by MALDI-TOF MS with high-energy CID (2011)
  • Author(s): Tanaka, K., Yamada, M., Tamiya-Koizumi, K., Kannagi, R., Aoyama, T., Hara, A., and Kyogashima, M.
  • Journal Title: Glycoconj. J Volume: 28 Issue: 2 Pages: 67-87
  • DOI: 10.1007/s10719-011-9325-6
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewisx expression and accelerates proliferation of colon cancer cells (2010)
  • Author(s): Yusa, A., Miyazaki, K., Kimura, N., Izawa, M., and Kannagi, R.
  • Journal Title: Cancer Res Volume: 70 Issue: 10 Pages: 4064-4073
  • DOI: 10.1158/0008-5472.can-09-2383
  • Peer Reviewed
• [Journal Article] Expression of CC-chemokine receptor 7(CCR7) and CXC-chemokine receptor 4(CXCR4) in head and neck squamous cell carcinoma (2010)
  • Author(s): Ueda, M., Shimada, T., Goto, Y., Tei, K., Nakai, S., Hisa, Y., and Kannagi, R
  • Journal Title: Auris Nasus Larynx Volume: 37 Issue: 4 Pages: 488-495
  • DOI: 10.1016/j.anl.2009.11.012
  • Peer Reviewed
• [Journal Article] Altered expression of glycan genes in cancers induced by epigenetic silencing and tumor hypoxia : Clues in the ongoing search for new tumor markers (2010)
  • Author(s): Kannagi, R., Sakuma, K., Miyazaki, K., Lim, K-T., Yusa, A., Yin, J., and Izawa, M.
  • Journal Title: Cancer Sci Volume: 101 Issue: 3 Pages: 586-593
  • DOI: 10.1111/j.1349-7006.2009.01455.x
  • NAID: 10026588975
  • Peer Reviewed
• [Journal Article] Glycosphingo-lipids as mediators of phenotypic changes associated with development and cancer progression (2010)
  • Author(s): Igarashi, Y. and Kannagi, R.
  • Journal Title: J. Biochem Volume: 147 Issue: 1 Pages: 3-8
  • DOI: 10.1093/jb/mvp195
  • NAID: 10027872823
  • Peer Reviewed
• [Journal Article] Expression of CC-chemokine receptor 7 (CCR7) and CXC-chemokine receptor 4 (CXCR4) in head and neck squamous cell carcinoma (2010)
  • Author(s): Ueda, M., et al.
  • Journal Title: Auris Nasus Larynx Volume: 37 Pages: 488-495
  • Peer Reviewed
• [Journal Article] Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewis^x expression and accelerates proliferation of colon cancer cells (2010)
  • Author(s): Yusa, A., et al.
  • Journal Title: Cancer Res. Volume: 70 Pages: 4064-4073
  • Peer Reviewed
• [Journal Article] Altered expression of glycan genes in cancers induced by epigenetic silencing and tumor hypoxia : Clues in the ongoing search for new tumor markers (2010)
  • Author(s): Kannagi, R., et al.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 586-593
  • NAID: 10026588975
  • Peer Reviewed
• [Journal Article] Altered sphingolipid metabolism induced by tumor hypoxia-new vistas of glycolipid tumor markers. (2010)
  • Author(s): Yin, J., et al.
  • Journal Title: FEBS Lett. 584 Pages: 1872-1878
  • Peer Reviewed
• [Journal Article] Acute kidney injury induced by protein-overload nephro-pathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides (2009)
  • Author(s): Zhang, X., Nakajima, T., Kamijo, Y., Li, G., Hu, R., Kannagi, R., Kyogashima, M., Aoyama, T., and Hara, A.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 390 Issue: 4 Pages: 1382-1388
  • DOI: 10.1016/j.bbrc.2009.10.164
  • NAID: 120007110394
  • Peer Reviewed
• [Journal Article] Expression of sialyl Lex, sialyl Lea, Lex and Ley glycotopes in secreted human ovarian cyst glycoproteins (2009)
  • Author(s): Yang, Z., Wu, J. H., Kuo, H. W., Kannagi, R., and Wu, A. M.
  • Journal Title: Biochimie Volume: 91 Issue: 3 Pages: 423-433
  • DOI: 10.1016/j.biochi.2008.11.002
  • Peer Reviewed
• [Journal Article] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in a RAPL-dependent and independent manner (2009)
  • Author(s): Ebisuno, T., Katagiri, K., Katakai, T., Ueda, Y., Nemoto, T., Inada, H., Nabekura, J., Okada, T., Kannagi, R., Tanaka, T., Miyasaka, M., Hogg, N., and Kinashi, T.
  • Journal Title: Blood Volume: 115 Issue: 4 Pages: 804-814
  • DOI: 10.1182/blood-2009-03-211979
  • Peer Reviewed
• [Journal Article] Altered sphingolipid metabolism induced by tumor hypoxia-new vistas of glycolipid tumor markers (2009)
  • Author(s): Yin, J., Miyazaki, K., Shaner, R. L., Merrill, A. H. Jr., and Kannagi, R.
  • Journal Title: FEBS Lett Volume: 584 Issue: 9 Pages: 1872-1878
  • DOI: 10.1016/j.febslet.2009.11.019
  • Peer Reviewed
• [Journal Article] Anti-oligosaccharide antibodies as tools for studying sulfated sialoglycoconjugate ligands for siglecs and selectins (2009)
  • Author(s): Kannagi, R., Ohmori, K., and Kimura, N.
  • Journal Title: Glycoconj. J. Volume: 26 Issue: 8 Pages: 923-928
  • DOI: 10.1007/s10719-008-9122-z
  • Peer Reviewed
• [Journal Article] Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides. (2009)
  • Author(s): Zhang, X., et al.
  • Journal Title: Biochem. Biophys. Res.Commun 390 Pages: 1382-1388
  • Peer Reviewed
• [Journal Article] Anti-oligosaccharide antibodies as tools for studying sulfated sialoglyco-njugate ligands for siglecs and selectins. (2009)
  • Author(s): Kannagi, R., et al.
  • Journal Title: Glycoconj.J. 26 Pages: 923-928
  • Peer Reviewed
• [Presentation] 最近の腫瘍マーカー糖鎖研究の展望 (2011)
  • Author(s): 神奈木玲児
  • Organizer: 第31回日本分子腫瘍マーカー研究会特別講演
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-02
• [Presentation] Biology of Sugar Modification (2011)
  • Author(s): Kannagi R.
  • Organizer: The 3rd Workshop of the Netherlands-Japan on Recent Advances in Glycobiology
  • Place of Presentation: Nagoya, Japan
• [Presentation] Role of glycan ligands for selectins and siglecs in cancer progression and metastasis (2011)
  • Author(s): Kannagi R
  • Organizer: International Symposium on Inflammation and Disease
  • Place of Presentation: Academia Sinica, Taipei, Taiwan
• [Presentation] Cell surface glycoconjugates involved in human lymphocytes homing of bronchial asthma and atopic dermatitis patients (2011)
  • Author(s): Kannagi R
  • Organizer: The Uehara Memorial Foundation Symposium-2011
  • Place of Presentation: Tokyo, Japan
• [Presentation] Biology of Sugar Modification (2011)
  • Author(s): Kannagi R.
  • Organizer: The 3^<rd> Workshop of the Netherlands-Japan on Recent Advances in Glycobiology
  • Place of Presentation: Nagoya, Japan
• [Presentation] 糖鎖と腫瘍マーカー (2010)
  • Author(s): 神奈木玲児
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪市)
• [Presentation] Sulfated carbohydrate ligands for selectins and siglecs (2010)
  • Author(s): Kannagi R
  • Organizer: The 28th Naito Conference on Glycan Expression and Regulation
  • Place of Presentation: Shonan Village Center, Kanagawa, Japan
• [Presentation] Carbohydrate-mediated cell adhesion involved in pathogenic homing behaviors of T-and B-lymphocytes (2009)
  • Author(s): Kannagi R, Sakuma K, Miyazaki K, Kimura N, Ohmori K
  • Organizer: 20th International Symposium on Glycoconjugates
  • Place of Presentation: Puerto Rico
  • Year and Date: 2009-12-29
• [Presentation] 糖鎖修飾と細胞認識 (2009)
  • Author(s): 神奈木玲児
  • Organizer: 第3回日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 名古屋市立大学医学部講堂(名古屋)
  • Year and Date: 2009-05-23
• [Presentation] 糖鎖修飾と細胞認識 (2009)
  • Author(s): 神奈木玲児
  • Organizer: 第3回日本生化学会中部支部例会・シンポジウム,日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 名古屋市
• [Book] 糖鎖抗原と腫瘍."臨床検査ガイド2011-2012" (2011)
  • Author(s): 神奈木玲児
  • Total Pages: 1082
  • Publisher: 文光堂
• [Book] Glycosylation changes in cancer.コールドスプリングハーバー糖鎖生物学第2版 (2010)
  • Author(s): Varki, A., Kannagi, R., and Toole, B. P
  • Total Pages: 651
  • Publisher: 丸善株式会社
• [Book] がん細胞に特有な糖鎖とそのはたらき."糖鎖を知る-その素顔と病気への挑戦" (2010)
  • Author(s): 神奈木玲児
  • Total Pages: 244
  • Publisher: 科学技術振興機構
• [Book] コールドスプリングハーバー糖鎖生物学第2版 (2010)
  • Author(s): Varki, A., et al.
  • Publisher: 丸善株式会社
• [Book] がんの進展における糖鎖のはたらき."第3の生命鎖、糖鎖の謎が今、解る" (2009)
  • Author(s): 神奈木玲児
  • Total Pages: 248
  • Publisher: クバプロ社
• [Remarks]
  • URL: http://www.aichi-med-u.ac.jp/institute/outline/sentanigaku.html
• [Remarks]
  • URL: http://www.aichi-med-u.ac.jp/institute/outline/sentanigaku.html
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/400/420/421/421-07.html
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/english/s-report/06_07/07mp.html