High Expression of N-acetylglucosaminyltransferase IVa Promotes Invasion of Choriocarcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2012 Nov 22

PMID 23169300

Citations 15

Authors

K Niimi

E Yamamoto

S Fujiwara

K Shinjo

T Kotani

T Umezu

H Kajiyama

K Shibata

K Ino

F Kikkawa

Affiliations

Soon will be listed here.

Abstract

Background: Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses β1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG.

Methods: We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo.

Results: The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of β1,4-N-acetylglucosamine branching on β1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of β1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth.

Conclusion: These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of β1 integrin.

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References

Mano Y, Shibata K, Sumigama S, Hayakawa H, Ino K, Yamamoto E . Tocilizumab inhibits interleukin-6-mediated matrix metalloproteinase-2 and -9 secretions from human amnion cells in preterm premature rupture of membranes. Gynecol Obstet Invest. 2009; 68(3):145-53. DOI: 10.1159/000229021. View

Schmid P, Nagai Y, Agarwal R, Hancock B, Savage P, Sebire N . Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet. 2009; 374(9683):48-55. DOI: 10.1016/S0140-6736(09)60618-8. View

Inamori K, Gu J, Ohira M, Kawasaki A, Nakamura Y, Nakagawa T . High expression of N-acetylglucosaminyltransferase V in favorable neuroblastomas: Involvement of its effect on apoptosis. FEBS Lett. 2006; 580(2):627-32. DOI: 10.1016/j.febslet.2005.12.089. View

Gu J, Isaji T, Sato Y, Kariya Y, Fukuda T . Importance of N-glycosylation on alpha5beta1 integrin for its biological functions. Biol Pharm Bull. 2009; 32(5):780-5. DOI: 10.1248/bpb.32.780. View

Kobata A, Takeuchi M . Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin. Biochim Biophys Acta. 1999; 1455(2-3):315-26. DOI: 10.1016/s0925-4439(99)00060-5. View

Hakomori S . Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res. 1989; 52:257-331. DOI: 10.1016/s0065-230x(08)60215-8. View

Baumann M, Deborde S, Illsley N . Placental glucose transfer and fetal growth. Endocrine. 2003; 19(1):13-22. DOI: 10.1385/ENDO:19:1:13. View

Ino K, Goto S, Kosaki A, Nomura S, Asada E, Misawa T . Growth inhibitory effect of bestatin on choriocarcinoma cell lines in vitro. Biotherapy. 1991; 3(4):351-7. DOI: 10.1007/BF02221328. View

Norris W, Nevers T, Sharma S, Kalkunte S . Review: hCG, preeclampsia and regulatory T cells. Placenta. 2011; 32 Suppl 2:S182-5. PMC: 3061407. DOI: 10.1016/j.placenta.2011.01.009. View

10.

Takamatsu S, Katsumata T, Inoue N, Watanabe T, Fujibayashi Y, Takeuchi M . Abnormal biantennary sugar chains are expressed in human chorionic gonadotropin produced in the choriocarcinoma cell line, JEG-3. Glycoconj J. 2004; 20(7-8):473-81. DOI: 10.1023/B:GLYC.0000038293.37376.9f. View

11.

Cole L, Birken S, Perini F . The structures of the serine-linked sugar chains on human chorionic gonadotropin. Biochem Biophys Res Commun. 1985; 126(1):333-9. DOI: 10.1016/0006-291x(85)90610-2. View

12.

Graham C, Hawley T, Hawley R, MacDougall J, Kerbel R, Khoo N . Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res. 1993; 206(2):204-11. DOI: 10.1006/excr.1993.1139. View

13.

Yamashita K, Totani K, Iwaki Y, Takamisawa I, Tateishi N, Higashi T . Comparative study of the sugar chains of gamma-glutamyltranspeptidases purified from human hepatocellular carcinoma and from human liver. J Biochem. 1989; 105(5):728-35. DOI: 10.1093/oxfordjournals.jbchem.a122736. View

14.

Yoshida A, Minowa M, Takamatsu S, Hara T, Oguri S, Ikenaga H . Tissue specific expression and chromosomal mapping of a human UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1, 4-N-acetylglucosaminyltransferase. Glycobiology. 1999; 9(3):303-10. DOI: 10.1093/glycob/9.3.303. View

15.

Soper J . Gestational trophoblastic disease. Obstet Gynecol. 2006; 108(1):176-87. DOI: 10.1097/01.AOG.0000224697.31138.a1. View

16.

Yamamoto E, Ito T, Abe A, Sido F, Ino K, Itakura A . Ikaros is expressed in human extravillous trophoblasts and involved in their migration and invasion. Mol Hum Reprod. 2005; 11(11):825-31. DOI: 10.1093/molehr/gah239. View

17.

Guibourdenche J, Handschuh K, Tsatsaris V, Gerbaud P, Leguy M, Muller F . Hyperglycosylated hCG is a marker of early human trophoblast invasion. J Clin Endocrinol Metab. 2010; 95(10):E240-4. DOI: 10.1210/jc.2010-0138. View

18.

Kajii T, Ohama K . Androgenetic origin of hydatidiform mole. Nature. 1977; 268(5621):633-4. DOI: 10.1038/268633a0. View

19.

Endo T, Nishimura R, Kawano T, Mochizuki M, Kobata A . Structural differences found in the asparagine-linked sugar chains of human chorionic gonadotropins purified from the urine of patients with invasive mole and with choriocarcinoma. Cancer Res. 1987; 47(19):5242-5. View

20.

Yamamoto E, Ino K, Miyoshi E, Shibata K, Takahashi N, Kajiyama H . Expression of N-acetylglucosaminyltransferase V in endometrial cancer correlates with poor prognosis. Br J Cancer. 2007; 97(11):1538-44. PMC: 2360248. DOI: 10.1038/sj.bjc.6604044. View