Tracking mannose-6-phosphorylated glycoproteins in cancer and inflammation
- Department of Molecular Sciences, Macquarie University, Sydney, Australia.
- UISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic -Universitat de Barcelona, Barcelona, Spain.
- Institute of Biomedical Sciences, University of Sau Paulo, Brazil.
Mannose-6-phosphate (M6P) is a modification of N-glycoproteins facilitating the trafficking of lysosomal hydrolases via the ER-Golgi network. Recently, extracellular roles of M6P-glycoproteins were suggested including their involvement in cell-to-cell communication and cell growth as indicated by the surface expression of M6P-receptors in inflammation and cancer. However, solid structural data is unavailable to assess the global M6P-glycoprotein expression. Herein, we have utilized quantitative LC-MS/MS-based glycomics to map, in an unbiased way, the presence of M6P-modified N-glycans from extra- and intra-cellular human glycoproteins derived from various cancer (e.g. prostate and breast) and immune (neutrophil) cells, tissues and bodily fluids (e.g. cystic fibrosis sputum). This interrogation revealed a hitherto unknown heterogeneity of N-glycans receiving M6P modifications and demonstrated both mono- and di-M6P additions to extracellular and subcellular-specific glycoproteins. Collectively, these findings add support for the involvement of M6P-glycoproteins in processes relating to inflammation and cancer.