Identification of potential marker of cancer stem cell from ovarian clear cell carcinoma

• Project/Area Number: 23592471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: SUZUKI KICHIYA 東北大学, 東北メディカル・メガバンク機構, 准教授 (30422116)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Kazunori 宮城県立がんセンター, 発がん制御研究部, 主任研究員 (80373215)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵巣癌 / がん幹細胞 / 表面マーカー / 免疫不全マウス / フローサイトメトリー

Research Abstract

Ovarian cancer frequently demonstrates chemotherapy-resistant mechanism and it has been recently reported that cancer stem cell is involved in this mechanism. We have planned to determine potential marker for cancer stem cell of ovarian cancer. We have chosen two ovarian cancer cell lines out of nine ovarian cancer cell lines based on tumor growth activity using immune deficient mice experiment (NOG mice). We have searched several potential marker for cancer stem cell and found that EpCAM negative population demonstrates high growth rate when inoculated to NOG mice. We have established EpCAM knock-down cell lines under doxycycline control. Unexpectedly the cell lines demonstrate growth inhibition when EpCAM expression was decresed. These data obtained from in vivo and in vitro experiments show some discrepancy however the mechanism is still unclear.

Research Products

• [Journal Article] Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma. (2014)
  • Author(s): Tamai K, Nakamura M, Mizuma M, Mochizuki M, Yokoyama M, Endo H, Yamaguchi K, Nakagawa T, Shiina M, Unno M, Muramoto K, Sato I, Satoh K, Sugamura K, Tanaka N.
  • Journal Title: Cancer Sci Volume: Mar 26
  • Peer Reviewed
• [Journal Article] Decreased Expression of 14-3-3<i>σ</i> Is Predictive of Poor Prognosis for Patients with Human Uterine Papillary Serous Carcinoma (2013)
  • Author(s): 1. Suzuki F, Nagase S, Suzuki K, Oba E, Hiroki E, Matsuda Y, Akahira J, Nishigori H, Sugiyama T, Otsuki T, Yoshinaga K, Takano T, Niikura H, Ito K, Sasano H, and Yaegashi N
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 231 Issue: 3 Pages: 193-199
  • DOI: 10.1620/tjem.231.193
  • NAID: 130004720755
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Molecular cloning and biochemical characterization of two novel Neu3 sialidases, neu3a and neu3b, from medaka (Oryzias latipes) (2013)
  • Author(s): Shiozaki K, Takeshita K, Ikeda M, Ikeda A, Harasaki Y, Komatsu M, Yamada S, Yamaguchi K, Miyagi T
  • Journal Title: Biochimie Volume: 95 Issue: 2 Pages: 280-289
  • DOI: 10.1016/j.biochi.2012.09.026
  • Peer Reviewed
• [Journal Article] Decreased Expression of 14-3-3σ is Predictive of Poor Prognosis for Patients with Human Uterine Papillary Serous Carcinoma. (2013)
  • Author(s): Suzuki F, Nagase S, Suzuki K, Oba E, Hiroki E, Matsuda Y, Akahira J, Nishigori H, Sugiyama T, Otsuki T, Yoshinaga K, Takano T, Niikura H, Ito K, Sasano H, and Yaegashi N.
  • Journal Title: Tohoku J Exp Med Volume: 231 Pages: 193-199
  • NAID: 130004720755
  • Peer Reviewed
• [Journal Article] Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. (2013)
  • Author(s): Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] CD271 defines a stem cell-like population in hypopharyngeal cancer. (2013)
  • Author(s): Imai T, Tamai K, Oizumi S, Oyama K, Yamaguchi K, Sato I, Satoh K, Matsuura K, Saijo S, Sugamura K, Tanaka N.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] DNA demethylation-dependent AR recruitment and GATA factors drive Rhox5 homeobox gene transcription in the epididymis (2012)
  • Author(s): Bhardwaj A, Song HW, Beildeck M, Kerkhofs S, Castoro R, Shanker S, De Gendt K, Suzuki K, Claessens F, Issa JP, Orgebin-Crist MC, Wilkinson MF.
  • Journal Title: Mol Endocrinol Volume: 26 Issue: 4 Pages: 538-49
  • DOI: 10.1210/me.2011-1059
• [Journal Article] Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling (2012)
  • Author(s): Kawamura, S., et al
  • Journal Title: Cell Death Differ Volume: 19 Issue: 1 Pages: 170-179
  • DOI: 10.1038/cdd.2011.83
  • Peer Reviewed
• [Journal Article] Structure, Biosynthesis and Function Sialic Acid Glycoconjugates in Health and Disease, 2012, 188-208 Joe Tiralongo and Ivan Martinez-Duncker (Eds) (2012)
  • Author(s): Suzuki T, Yamaguchi K
  • Journal Title: Bentham Science Publishers CHAPTER 6 Mammalian Sialidases.
• [Journal Article] Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons. 86 (2012)
  • Author(s): Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, Kitajima K, Higashi H, Nitta K, Shima H, Miyagi T
  • Journal Title: J Biol Chem Volume: 287 Pages: 14816-14826
• [Journal Article] Mammalian sialidases : physiological and pathological roles in cellular functions (2012)
  • Author(s): Miyagi, T., et al
  • Journal Title: Glycobiology Volume: 22 Issue: 7 Pages: 880-896
  • DOI: 10.1093/glycob/cws057
  • Peer Reviewed
• [Journal Article] Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase (2012)
  • Author(s): Yamaguchi K, Shiozaki K, Moriya S, Koseki K, Wada T, Tateno H, Sato I, Asano M, Iwakura Y, Miyagi T
  • Journal Title: PLoS One Volume: 7
• [Journal Article] Altered expression of sialidases in human cancer (2012)
  • Author(s): Miyagi T, Takahashi K, Moriya S, Hata K, Yamamoto K, Wada T, Yamaguchi K, Shiozaki K
  • Journal Title: Adv Exp Med Biol Volume: 749 Pages: 257-267
  • DOI: 10.1007/978-1-4614-3381-1_17
  • ISBN: 9781461433804, 9781461433811
  • Peer Reviewed
• [Journal Article] Human cytosolic sialidase NEU2-low general tissue expression but involvementin PC-3 prostate cancer cell survival (2012)
  • Author(s): Koseki K, Wada T, Hosono M, Hata K, Yamaguchi K, Nitta K, Miyagi T
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Issue: 1 Pages: 142-149
  • DOI: 10.1016/j.bbrc.2012.10.028
  • Peer Reviewed
• [Journal Article] DNA demethylation-dependent AR recruitment and GATA factors drive Rhox5 homeobox gene transcription in the epididymis. (2012)
  • Author(s): Bhardwaj A, Song HW, Beildeck M, Kerkhofs S, Castoro R, Shanker S, De Gendt K, Suzuki K, Claessens F, Issa JP, Orgebin-Crist MC, Wilkinson MF
  • Journal Title: Mol Endocrinol Volume: 26 Pages: 538-549
  • Peer Reviewed
• [Journal Article] Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase. (2012)
  • Author(s): Yamaguchi K, Shiozaki K, Moriya S, Koseki K, Wada T, Tateno H, Sato I, Asano M, Iwakura Y, Miyagi T.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Molecular cloning and biochemical characterization of two novel Neu3 sialidases, neu3a and neu3b, from medaka (Oryzias latipes). (2012)
  • Author(s): Shiozaki K, Takeshita K, Ikeda M, Ikeda A, Harasaki Y, Komatsu M, Yamada S, Yamaguchi K, Miyagi T.
  • Journal Title: Biochimie Volume: 95 Pages: 280-289
  • Peer Reviewed
• [Journal Article] Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons. (2012)
  • Author(s): Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, Kitajima K, Higashi H, Nitta K, Shima H, Miyagi T.
  • Journal Title: J Biol Chem Volume: 287 Pages: 14816-14826
  • Peer Reviewed
• [Journal Article] Altered expression of sialidases in human cancer. (2012)
  • Author(s): Miyagi T, Takahashi K, Moriya S, Hata K, Yamamoto K, Wada T, Yamaguchi K, Shiozaki K.
  • Journal Title: Adv Exp Med Biol Volume: 749 Pages: 257-267
  • Peer Reviewed
• [Journal Article] Sialidase significance for cancer progression. (2012)
  • Author(s): Miyagi T, Takahashi K, Hata K, Shiozaki K, Yamaguchi K.
  • Journal Title: Glycoconj J Volume: 29 Pages: 567-577
  • Peer Reviewed
• [Journal Article] Mammalian sialidases: physiological and pathological roles in cellular functions. (2012)
  • Author(s): Miyagi T, Yamaguchi K.
  • Journal Title: Glycobiology Volume: 22 Pages: 880-896
  • Peer Reviewed
• [Journal Article] Human cytosolic sialidase NEU2-low general tissue expression but involvementin PC-3 prostate cancer cell survival. (2012)
  • Author(s): Koseki K, Wada T, Hosono M, Hata K, Yamaguchi K, Nitta K, Miyagi T.
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Pages: 142-149
  • Peer Reviewed
• [Journal Article] NA Demethylation-Dependent AR Recruitment and GATA Factors Drive Rhox5 Homeobox Gene Transcription in the Epididymis (2012)
  • Author(s): Bhardwaj A, Song HW, Beildeck M, Kerkhofs S, Castoro R, Shanker S, De Gendt K, Suzuki K, Claessens F, Issa JP, Orgebin-Crist MC, and Wilkinson MF
  • Journal Title: Mol Endocrinol. Volume: 26 Pages: 538-549
  • Peer Reviewed
• [Journal Article] Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4 (2011)
  • Author(s): Shiozaki, K., et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 24 Pages: 21052-21061
  • DOI: 10.1074/jbc.m111.231191
  • Peer Reviewed
• [Journal Article] シアリダーゼ、生物機能モデルと新しいリソースリサーチツール (2011)
  • Author(s): 山口壹範,宮城妙子
  • Journal Title: エルアイシー Pages: 340-345
  • URL: http://homepage3.nifty.com/lic/books/nbs09.html
• [Book] Structure, Biosynthesis and Function Sialic Acid Glycoconjugates in Health and Disease in Mammalian Sialidases CHAPTER 6 (Eds Tiralongo J and Martinez-Duncker I) (2012)
  • Author(s): Suzuki T and Yamaguchi K.
  • Publisher: Bentham Science Publishers