Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.

Abstract

Generally, most of ovarian cancer cannot be detected until large scale and remote metastasis occurs, which is the major cause of high mortality in ovarian cancer. Therefore, it is urgent to discover metastasis-related biomarkers for the detection of ovarian cancer in its occult metastasis stage. Altered glycosylation is a universal feature of malignancy and certain types of glycan structures are well-known markers for tumor progressions. Thus, this study aimed to reveal specific changes of N-glycans in the secretome of the metastatic ovarian cancer. We employed a quantitative glycomics approach based on metabolic stable isotope labeling to compare the differential N-glycosylation of secretome between an ovarian cancer cell line SKOV3 and its high metastatic derivative SKOV3-ip. Intriguingly, among total 17 N-glycans identified, the N-glycans with bisecting GlcNAc were all significantly decreased in SKOV3-ip in comparison to SKOV3. This alteration in bisecting GlcNAc glycoforms as well as its corresponding association with ovarian cancer metastatic behavior was further validated at the glycotransferase level with multiple techniques including real-time PCR, western blotting, transwell assay, lectin blotting and immunohistochemistry analysis. This study illustrated metastasis-related N-glycan alterations in ovarian cancer secretome in vitro for the first time, which is a valuable source for biomarker discovery as well. Moreover, N-glycans with bisecting GlcNAc shed light on the detection of ovarian cancer in early peritoneal metastasis stage which may accordingly improve the prognosis of ovarian cancer patients.

• Authors: Xingwang Zhang, Yisheng Wang, Yifan Qian, Xin Wu, Zejian Zhang, Xijun Liu, Ran Zhao, Lei Zhou, Yuanyuan Ruan, Jiejie Xu, Haiou Liu, Shifang Ren, Congjian Xu, Jianxin Gu
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e87978 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24516574 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrogen Isotopes
• Polysaccharides
• N-Acetylglucosaminyltransferases
• beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase

Topics

• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cell Movement
• Female
• Gene Knockdown Techniques
• Glycomics (methods)
• Humans
• Immunohistochemistry
• Middle Aged
• N-Acetylglucosaminyltransferases (metabolism)
• Neoplasm Grading
• Neoplasm Metastasis
• Neoplasms, Glandular and Epithelial (metabolism, pathology)
• Nitrogen Isotopes
• Ovarian Neoplasms (metabolism, pathology)
• Polysaccharides (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization