Trimannosyl structure on stem cells and carcinomas/inflamed tissue recognized by Mannitou antibody

We have developed a monoclonal antibody called Mannitou that recognizes highly specific the trimannosyl core structure typically found in eukaryotic N-glycans. When screened against the glycan array generated by the Consortium for Functional Glycomics (USA) Mannitou was found to exhibit strongly reduced binding when the trimannosyl structure was modified with any further monosaccharide. Trimannosyl (“paucimannose”) is not a structure commonly reported for mammalian tissue. The hypothesis that pauci-mannose results from enzyme changes in the early glycosylation pathway is consistent with the abundant mannosidic glycans seen in mass spectrometry data from different types of cancer cell lines.

Mannitou antibody intensely labels the surface of human adult pancreatic stem cells and pancreatic cancer cell lines. Within inflamed mouse pancreata, it labels the exocrine ducts, the site of adult stem cells. The failure of Mannitou antibody to bind to normal, non-tumorigenic cells other than stem cells, under the same conditions, indicates its specificity for stemness/cancer/inflammation.

To investigate expression of the trimannosyl structure in mouse brain, different postnatal stages were analysed. We found that at early postnatal stages (P0-P4) the trimannosyl structure is specifically expressed on neural precursor cells of the SVZ-RMS-OB system. At later stages this structure is downregulated in the rostral migratory stream (RMS) and olfactory bulb (OB) but remains in the subventricular zone (SVZ). These data might point to a role of the trimannosyl structure in neural stem cells of postnatal mouse brain.