Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Protein paucimannosylation is an enriched N-glycosylation signature of human cancers (#22)

Sayantani Chatterjee 1 , Ling Y. Lee 2 , Rebeca Kawahara 3 , Jodie L. Abrahams 4 , Barbara Adamczyk 5 , Merrina Anugraham 6 , Christopher Ashwood 7 , Zeynep Sumer-Bayraktar 8 , Matthew T. Briggs 9 , Jenny H.L. Chik 10 , Arun Everest-Dass 4 , Sarah Förster 11 , Hannes Hinneburg 1 , Katia R.M. Leite 12 , Ian Loke 13 , Uwe Möginger 14 , Edward S.X. Moh 1 , Miyako Nakano 15 , Saulo Recuero 12 , Manveen K. Sethi 16 , Miguel Srougi 12 , Kathrin Stavenhagen 17 , Vignesh Venkatakrishnan 18 , Katherine Wongtrakul-Kish 19 , Simone Diestel 20 , Peter Hoffmann 9 , Niclas G. Karlsson 5 , Daniel Kolarich 4 , Mark P. Molloy 21 , Michael H. Muders 11 , Martin K. Oehler 22 , Nicolle H. Packer 1 , Giuseppe Palmisano 3 , Morten Thaysen-Andersen 1
  1. Department of Molecular Sciences and Biomolecular Discovery and Design Research Centre (BDDRC), , Macquarie University, Sydney, New South Wales, Australia
  2. ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic -Universitat de Barcelona, Barcelona, Spain
  3. Department of Parasitology, Institute of Biomedical Sciences, University of Sau Paulo, Sau Paulo, Brazil
  4. Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
  5. Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy,, University of Gothenburg,, Gothenburg, Sweden
  6. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  7. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, USA
  8. School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
  9. Future Industries Institute, Mawson Lakes Campus, University of South Australia, Adelaide, South Australia, Australia
  10. International Collaboration On Repair Discoveries (ICORD), Vancouver Coastal Health Research Institute and Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, Canada
  11. Rudolf-Becker-Laboratory, Institute of Pathology, University Hospital Bonn, Bonn, Germany
  12. Laboratório de Investigação Médica da Disciplina de Urologia (LIM55), Faculdade de Medicina da FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
  13. Department of Biological Sciences, National University of Singapore, Singapore
  14. Institute for Biochemistry and Molecular Biology, University of Southern Denmark, Denmark
  15. Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima, Japan
  16. Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine , Boston University, Boston, MA, USA
  17. Beth Israel Deaconess Medical Center, Department of Surgery and Harvard Medical School Center for Glycoscience, Harvard Medical School, Boston, MA, USA
  18. Department of Rheumatology & Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  19. Bioprocessing Technology Institute (BTI), A*STAR, Singapore
  20. Institute of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
  21. Sydney Medical School, Bowel Cancer and Biomarker Laboratory, Kolling Institute, The University of Sydney, Sydney, New South Wales, Australia
  22. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

We recently discovered an immune-related class of glycoproteins decorated with paucimannosidic N-glycans (PMGs) [Man(M)1-3GlcNAc2Fuc(F)0-1] expressed by innate immune cells [Thaysen-Andersen et al., J Biol Chem, 290(14):8789, 2015]. Herein, we extend these findings by investigating a possible association between protein paucimannosylation and cancer. To this end, the distribution of PMGs released from proteins expressed by a wide range of human cancer cells and tissues and matching non-cancerous specimens were determined by re-interrogating a large collection of published and unpublished N-glycomics datasets acquired over a decade within our laboratories using a uniform porous graphitised carbon liquid chromatography tandem mass spectrometry method. The total level of PMGs within the entire N-glycome and the relative distribution of the individual PMG species (M1, M1F, M2, M2F, M3, and M3F) were accurately determined using this well-established quantitative glycomics platform. In total, N-glycome profiling data from 34 different cancer cell lines, and 133 tissue samples spanning 11 cancer types with matching non-cancerous specimens, were (re-) curated from 467 datasets. Although the total PMG levels varied dramatically across and within the investigated cancer types (1.0%-50.2%), particularly the α1,6-fucosylated bi- and tri-mannosylated N-glycans (M2F and M3F) were consistently prominent features of most of the cancer cell lines. Analyses of paired (tumour/non-tumour) and stage-stratified tissues demonstrated that PMGs are significantly enriched in tumours from several cancer types including non-melanoma skin cancer (p = 0.0145), liver (p = 0.0033) and colorectal (p = 0.0017) cancers and are increased with prostate cancer and chronic lymphocytic leukaemia progression (both p < 0.02). Based on these correlation-type observations we conclude that protein paucimannosylation represents a significant, but non-uniform, glycoepitope of human cancers. These findings advance our understanding of the glyco-features expressed by human cancers and encourage further cause-effect type studies of paucimannosylation in cancer tumorigenesis and metastasis.