Pathobiology of glycans involved in cancer invasion and metastasis

2009 Fiscal Year Final Research Report

• Project/Area Number: 17015051
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: KANNAGI Reiji Aichi Cancer Center Research Institute, 分子病態学部, 部長 (80161389)
• Co-Investigator(Kenkyū-buntansha): TAKU Reisei 愛知医科大学, 医学部, 准教授 (00399031) ; TAGUCHI Osamu 愛知県がんセンター(研究所), 分子病態学部, 室長 (00142167) ; GOTO Yoshiko 愛知県がんセンター(研究所), 分子病態学部, 技師 (30416169)
• Co-Investigator(Renkei-kenkyūsha): TAGUCHI Osamu 愛知県がんセンター(研究所), 分子病態学部, 室長 (00142167) ; YUSA Akiko 愛知県がんセンター(研究所), 分子病態学部, リサーチレジデント (00455536)
• Project Period (FY): 2005 – 2009
• Keywords: セレクチン / CD44 / ヒアルロン酸 / エピジェネティック・サイレンシング / hypoxia induciblefactor(HIF) / シアリルルイスX / シアリルルイスa / 細胞接着分子

Research Abstract

細胞表層の糖鎖には接着分子としての機能を持つものがある。癌細胞ではシアリルルイスXやシアリルルイスaなどの糖鎖が発現し、これによって転移や浸潤が引き起こされる。癌細胞で糖鎖が変化する機構は、発癌早期においては、正常型糖鎖を合成する一連の遺伝子のエピジェネティック・サイレンシングが主原因の一つとなっていることを我々は明らかにした。一方、進行期の癌においては、癌細胞の低酸素抵抗性の獲得とともに機能亢進する転写因子hypoxia inducible factor(HIF)が、一連の糖鎖合成遺伝子の転写を誘導することが大きな要因となっていることを我々は明らかにした。

Research Products

• [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., Izawa, M.
  • Journal Title: Cancer Sci. CancerSci. Pages: 586-593
• [Journal Article] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in a RAPL-dependent and independent manner. (2010)
  • 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., Kinashi, T.
  • Journal Title: Blood 115 Pages: 804-814
• [Journal Article] Inter-α-trypsin inhibitor promotes bronchial epithelial repair after injury through vitronectin binding. (2009)
  • Author(s): Adair, J.E., Stober, V., Sobhany, M., Zhuo, L., Roberts, J.D., Negishi, M., Kimata, K., Garantziotis, S.
  • Journal Title: J. Biol. Chem. 284 Pages: 16922-16930
• [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., Wu, A.M.
  • Journal Title: Biochimie 91 Pages: 423-433
• [Journal Article] Significance of NF-κB/GATA axis in TNF-α-induced expression of 6-sulfated cell-recognition glycans in human T-lymphocytes. (2008)
  • Author(s): Chen, G. -Y., Sakuma, K., Kannagi, R.
  • Journal Title: J. Biol. Chem. 283 Pages: 34563-34570
• [Journal Article] Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants- Biochim. (2008)
  • Author(s): Kannagi, R., Yin, J., Miyazaki, K., Izawa, M.
  • Journal Title: Biophys. Acta 1780 Pages: 525-531
• [Journal Article] DNA hypermethylation contributes to incomplete synthesis of carbohydrate determinants in gastrointestinal cancer. (2008)
  • Author(s): Kawamura, Y.I., Toyota, M., Kawashima, R., Hagiwara, T., Suzuki, H., Imai, K., Shinomura, Y., Tokino, T., Kannagi, R., Dohi, T.
  • Journal Title: Gastroenterology 135 Pages: 142-151
• [Journal Article] CD43, but not P-selectin glycoprotein ligand-1, functions as an E-selectin counter-receptor in human pre-B-cell leukemia NALL-1. (2008)
  • Author(s): Nonomura, C., Kikuchi, J., Kiyokawa, N., Ozaki, H., Mitsunaga, K., Ando, H., Kanamori, A., Kannagi, R., Fujimoto, J., Muroi, K., Furukawa, Y., Nakamura, M.
  • Journal Title: Cancer Res. 68 Pages: 790-799
• [Journal Article] Clinical application of functional glycoproteomics - dissection of glycotopes carried by soluble CD44 variants in sera of patients with cancers. (2008)
  • Author(s): Lim, K-T., Miyazaki, K., Kimura, N., Izawa, M., Kannagi, R.
  • Journal Title: Proteomics 8 Pages: 3263-3273
• [Journal Article] Human B-lymphocytes expressα2-6 sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/siglec-2. (2007)
  • Author(s): Kimura, N., Ohmori, K., Miyazaki, K., Izawa, M., Matsuzaki, Y., Yasuda, Y., Takematsu, H., Kozutsumi, Y., Moriyama, A., Kannagi, R.
  • Journal Title: J. Biol. Chem. 282 Pages: 32200-32207
• [Journal Article] Hyperproduction of hyaluronan in Neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: Possible involvement of versican/PG-M. (2007)
  • Author(s): Koyama, H., Hibi, T., Isogai, Z., Yoneda, M., Fujimori, M., Amano, J., Kawakubo, M., Kannagi, R., Kimata, K., Taniguchi, S., Itano, N.
  • Journal Title: Am. J. Pathol. 170 Pages: 1086-1099
• [Journal Article] Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded dendritic cells and tumor antigen DNA. (2007)
  • Author(s): Teramoto, K., Kontani, K., Fujita, T., Ozaki, Y., Sawai, S., Tezuka, N., Fujino, S., Itoh, Y., Taguchi, O., Kannagi, R., Ogasawara, K.
  • Journal Title: Cancer Immunol. Immunother. 56 Pages: 331-342
• [Journal Article] Glycomic mapping of pseudomucinous human ovarian cyst glycoproteins: Identification of Lewis and sialyl Lewis glycotopes. (2007)
  • Author(s): Wu, A.M., Khoo, K.H., Yu, S.Y., Yang, Z., Kannagi, R., Watkins, W.M.
  • Journal Title: Proteomics 7 Pages: 3699-3717
• [Journal Article] nteraction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. (2006)
  • Author(s): Chen, G. -Y., Osada, H., Santamaria- Babi, L.F., Kannagi, R.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 103 Pages: 16894-16899
• [Journal Article] Molecular cloning and characterization of a novel 3'-phosphoadenosine 5'-phosphosulfate transporter (2006)
  • Author(s): Kamiyama, S., Sasaki, N., Goda, E., Ui-Tei, K., Saigo, K., Narimatsu, H., Jigami, Y., Kannagi, R., Irimura, T., Nishihara, S.
  • Journal Title: PAPST2. J. Biol. Chem. 281 Pages: 10945-10953
• [Journal Article] Rapid demonstration of diversity of sulfatide molecular species from biological materials by MALDI-TOF MS. (2006)
  • Author(s): Kyogashima, M., Tamiya-Koizumi, K., Ehara, T., Li, G., Hu, R., Hara, A., Aoyama, T., Kannagi, R.
  • Journal Title: Glycobiology 16 Pages: 719-728
• [Journal Article] Identification of cutaneous lymphocyte- associated antigen as sialyl 6-sulfo Lewis x, a selectin ligand expressed on a subset of skin-homing helper memory T cells. (2006)
  • Author(s): Ohmori, K., Fukui, F., Kiso, M., Imai, T., Yoshie, O., Hasegawa, H., Matsushima, K., Kannagi, R.
  • Journal Title: Blood 107 Pages: 3197-3204
• [Journal Article] Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells. (2006)
  • Author(s): Yin, J., Hashimoto, A., Izawa, M., Miyazaki, K., Chen, G. -Y., Takematsu, H., Kozutsumi, Y., Suzuki, A., Furuhata, K., Cheng, F. -L., Lin, C. -H., Sato, C., Kitajima, K., Kannagi, R.
  • Journal Title: Cancer Res. 66 Pages: 2937-2945
• [Journal Article] SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. (2006)
  • Author(s): Zhuo, L., Kanamori, A., Kannagi, R., Itano, N., Wu, J., Hamaguchi, M., Ishiguro, N., Kimata, K.
  • Journal Title: J. Biol. Chem. 281 Pages: 20303-20314
• [Journal Article] Synthesis of {α}(1, 3)fucosyltransferases IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin. (2005)
  • Author(s): Satoh, T., Kanai, Y., Wu, M.H., Yokozeki, H., Kannagi, R., Lowe, J.B., Nishioka, K.
  • Journal Title: Am. J. Pathol. 167 Pages: 787-796
• [Journal Article] A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules. (2005)
  • Author(s): Uchimura, K., Gauguet, J.M., Singer, M.S., Tsay, D., Kannagi, R., Muramatsu, T., Von Andrian, U.H., Rosen, S.D.
  • Journal Title: Nat. Immunol. 6 Pages: 1105-1113
• [Journal Article] Development of structural analysis of sulfated N- glycans by multi-dimensional HPLC mapping methods. (2005)
  • Author(s): Yagi, H., Takahashi, N., Yamaguchi, Y., Kimura, N., Uchimura, K., Kannagi, R., Kato, K.
  • Journal Title: Glycobiology 15 Pages: 1051-1060
• [Presentation] Carbohydrate- mediated cell adhesion involved in pathogenic homing behaviors of Tand B-lymphocytes. (2009)
  • Author(s): Kannagi R, Sakuma K, Miyazaki K, Kimura N, Ohmori K
  • Organizer: 20th International Symposium on Glycoconjugates
  • Place of Presentation: San Juan, Puerto Rico
  • Year and Date: 20091129-20091204
• [Presentation] Roles of epigenetic gene silencing and tumor hypoxia in induction of cancer-associated carbohydrate determinants (2009)
  • Author(s): Kannagi R
  • Organizer: 2nd Seminar on Functional Glycomics, "Clinical and translational research on cancer: Glycomics application", (Chaired by Paulson J and Taniguchi N)
  • Place of Presentation: Toba, Japan
  • Year and Date: 20090324-20090327
• [Presentation] Sialylated and sulfated ligands on human B-lymphocytes for CD22/Siglec2 (2008)
  • Author(s): Kannagi R, Ohmori K, Sakuma K, Kimura N
  • Organizer: 12th International Conference on Biology and Chemistry of Sialic Acid (SialoGlycoT2008), (Chaired by N. V Bovin)
  • Place of Presentation: Moscow-St. Petersburg, Russia
  • Year and Date: 20080721-20080726
• [Presentation] Regulation of glycosyltransferase gene expression involved in lymphocyte homing (2008)
  • Author(s): Chen G-Y, Sakuma K, Kannagi R
  • Organizer: Sixth International Glycosyltransferase Conference (GlycoT2008), (Chaired by R. Cummings and M. Pierce)
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20080517-20080521
• [Presentation] Immunogenic GM2 ganglioside antigen on cancer cells (2008)
  • Author(s): Kannagi R
  • Organizer: Gordon Research Conferences 2008 "Glycolipid & Sphingolipid Biology", (Chaired by Gerrit Van Meer)
  • Place of Presentation: Lucca Italy
  • Year and Date: 20080217-20080222
• [Presentation] Hypoxia-induced expression of cancer-associated glycoconjugates (2007)
  • Author(s): Kannagi R
  • Organizer: The 27th Sapporo Cancer Seminar International Symposium "Glycomics: new perspectives in cancer cell behavior", (Chaired by N Taniguchi)
  • Place of Presentation: Sapporo
  • Year and Date: 20070712-20070714
• [Presentation] Selectin-mediated cell adhesion in cancer metastasis. (2007)
  • Author(s): Kannagi R
  • Organizer: 19th FAOBMB Conference, Symposium "Cell adhesion and migration" (Chaired by WK Song and JW Lee)
  • Place of Presentation: Seoul
  • Year and Date: 20070527-20070530
• [Presentation] Tumor hypoxia induces expression of carbohydrate determinants involved in adhesion of circulating cancer cells to vascular endothelium. (2006)
  • Author(s): Kannagi R
  • Organizer: The 11th International Congress of the Metastasis Research Society
  • Place of Presentation: Tokushima
  • Year and Date: 20060903-20060906
• [Presentation] Transcriptional regulation of ficosyltransferase VII, a rate-limiting enzyme for selectin ligand synthesis (2005)
  • Author(s): Kannagi R
  • Organizer: 2nd Workshop the Netherlands- Japan on Recent Advances in Glycobiology, Chaired by H.
  • Place of Presentation: Vliegenthart, Utrecht, The Netherland
  • Year and Date: 20050417-20050421
• [Book] Essentials of Glycobiology (2009)
  • Author(s): Varki, A., Kannagi, R., Toole, B.P. Glycosylation changes in cancer. In: A. Varki, R.D. Cummings, J.D. Esko, H.H. Freeze, G.W. Hart, J.D. Marth
  • Total Pages: 617-632
  • Publisher: Cold Spring Harbor Laboratory Press
• [Book] Roles of carbohydrate-mediated cell adhesion in cancer progression. In: N. Taniguchi, A. Suzuki, Y. Ito, H. et al. (eds. ) (2008)
  • Author(s): Kannagi, R., Seko, A.
  • Total Pages: 246-251
  • Publisher: Springer Japan
• [Book] Alteration of carbohydrate- mediated cell-cell interactions in cancers induced by epigenetic silencing of glycogenes. In: C. Sansom and O. Markman (eds. ) (2007)
  • Author(s): Kannagi, R., Miyazaki, K., Kimura, N., Yin, J.
  • Total Pages: 274-287
  • Publisher: Scion Publishing Ltd.
• [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