The lectin Helix pomatia agglutinin recognises O-GlcNAc containing glycoproteins in human breast cancer

Rambaruth, Neela D.S., Greenwell, Pamela and Dwek, Miriam (2012) The lectin Helix pomatia agglutinin recognises O-GlcNAc containing glycoproteins in human breast cancer. Glycobiology, 22 (6). pp. 839-848. ISSN 0959-6658

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There has been considerable interest in understanding the epitopes that bind the lectin Helix pomatia agglutinin (HPA) in breast cancer as the lectin has been shown to identify glycosylation changes associated with the development of metastatic disease. HPA has previously been shown to recognise aberrant O-linked ?-GalNAc / mucin glycosylation in cancer, including exposed Tn-epitopes. However, recent glycan-array analysis reported that diverse epitopes are also recognised by the lectin, for example, CFG data: GalNAc?1,3Gal; ?-GalNAc; GlcNAc?1,4Gal. The intriguing observations from the CFG array led to this study, in which HPA binding epitopes were localised and characterised in an in vitro model of breast cancer metastasis.HMT3522 (benign disease), BT474 (primary cancer) and T47D/ MCF7 (metastatic cancer) cells were assessed in confocal microscopy based co-localisation studies and a glycoproteomic analysis based on 2-DE, Western blotting and mass spectrometry (MS) was adopted. HPA binding correlated with levels of integrin ?6, transcription factors HnRNP H1, HnRNP D-like, HnRNP A2/B1 as well as Hsp27, GFAP and ENO1. These glycoproteins were non-detectable in the non-metastatic breast cancer cell lines. The recognition of HnRNPs, Hsp27 and ENO1 by HPA correlated with O-GlcNAcylation of these proteins. Integrin ?6 was the most abundant HPA glycoprotein in the breast cancer cells with a metastatic phenotype; this concurred with previous findings in colorectal cancer.This is the first report in which HPA has been shown to bind O-GlcNAcylated transcription factors. This class of proteins represent a new means by which HPA differentiates cancer cells with an aggressive metastatic phenotype.

Item Type: Article
Subjects: University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)
Depositing User: Miss Nina Watts
Date Deposited: 21 Feb 2012 11:58
Last Modified: 07 Jun 2012 10:27

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