Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei

被引:8
作者
Saarinen, Lilli [1 ]
Nummela, Pirjo [1 ]
Leinonen, Hannele [1 ]
Heiskanen, Annamari [2 ]
Thiel, Alexandra [1 ]
Haglund, Caj [3 ,4 ,5 ]
Lepisto, Anna [3 ,4 ]
Satomaa, Tero [2 ]
Hautaniemi, Sampsa [1 ]
Ristimaki, Ari [1 ,6 ,7 ]
机构
[1] Univ Helsinki, Res Programs Unit, Genome Scale Biol Res Program, POB 63, FI-00014 Helsinki, Finland
[2] Glykos Finland Ltd, Viikinkaari 6, FI-00790 Helsinki, Finland
[3] Univ Helsinki, Dept Surg, HUS, POB 440, FI-00029 Helsinki, Finland
[4] Helsinki Univ Hosp, HUS, POB 440, FI-00029 Helsinki, Finland
[5] Univ Helsinki, Res Programs Unit, Translat Canc Biol, POB 63, FI-00014 Helsinki, Finland
[6] Univ Helsinki, HUSLAB, Dept Pathol, HUS, POB 400, FI-00029 Helsinki, Finland
[7] Helsinki Univ Hosp, HUS, POB 400, FI-00029 Helsinki, Finland
基金
芬兰科学院;
关键词
HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; PAPILLARY MUCINOUS NEOPLASMS; CORE FUCOSYLATION; CYTOREDUCTIVE SURGERY; MOLECULAR PROFILES; LEWIS ANTIGENS; APPENDICEAL; EXPRESSION; MUTATIONS; SURVIVAL;
D O I
10.1074/mcp.RA118.000615
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Pseudomyxoma peritonel (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites. KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent. As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix. Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry. Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation. We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls. Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohis-tochemistry. We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene. Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP. Glycomic data are available via ProteomeXchange with identifier PXDO10086.
引用
收藏
页码:2107 / 2118
页数:12
相关论文
共 54 条
  • [51] Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling
    Wang, XC
    Gu, JG
    Ihara, H
    Miyoshi, E
    Honke, K
    Taniguchi, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (05) : 2572 - 2577
  • [52] Fucosylation is associated with the malignant transformation of intraductal papillary mucinous neoplasms: a lectin microarray-based study
    Watanabe, Kiminori
    Ohta, Masayuki
    Yada, Kazuhiro
    Komori, Yoko
    Iwashita, Yukio
    Kashima, Kenji
    Inomata, Masafumi
    [J]. SURGERY TODAY, 2016, 46 (10) : 1217 - 1223
  • [53] Deletion of core fucosylation on α3β1 integrin down-regulates its functions
    Zhao, Yanyang
    Itoh, Satsuki
    Wang, Xiangchun
    Isaji, Tomoya
    Miyoshi, Eiji
    Kariya, Yoshinobu
    Miyazaki, Kaoru
    Kawasaki, Nana
    Taniguchi, Naoyuki
    Gu, Jianguo
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (50) : 38343 - 38350
  • [54] Inhibition of fucosylation by 2-fluorofucose suppresses human liver cancer HepG2 cell proliferation and migration as well as tumor formation
    Zhou, Ying
    Fukuda, Tomohiko
    Hang, Qinglei
    Hou, Sicong
    Isaji, Tomoya
    Kameyama, Akihiko
    Gu, Jianguo
    [J]. SCIENTIFIC REPORTS, 2017, 7