Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Mapping protein paucimannosylation across human cancers (#120)

Sayantani Chatterjee 1 , Ling Y. Lee 2 , Merrina Anugraham 3 , Manveen K. Sethi 4 , Zeynep Sumer-Bayraktar 5 , Katherine Wongtrakul-Kish 6 , Jenny H.L. Chik 7 , Ian Loke 1 , Christopher Ashwood 1 , Rebeca K. Sakuma 1 8 , Miyako Nakano 9 , Simone Diestel 10 , Giuseppe Palmisano 8 , Mark P. Molloy 1 , Nicolle H. Packer 1 , Morten Thaysen-Andersen 1
  1. Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia
  2. ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital ClĂ­nic -Universitat de Barcelona, Barcelona, Spain
  3. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  4. Center for Biomedical Mass Spectrometry, Boston University, Boston, MA
  5. School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
  6. Bioprocessing Technology Institute, A*STAR, Singapore
  7. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver , BC, Canada
  8. Department of Parasitology, Institute of Biomedical Sciences, University of Sau Paulo, Sau Paulo, Brazil
  9. Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima, Japan
  10. Institute of Nutrition and Food Sciences, University of Bonn, Bonn, Germany

Protein paucimannosylation, a type of truncated N-glycosylation with the simple composition Man(M)1-3GlcNAc2Fuc(F)0-1, was previously considered an invertebrate- and plant-specific glycoepitope absent in mammals. However, we recently established that protein paucimannosylation is a significant feature of the human innate immune system1. We have also made scattered encounters of paucimannosidic glycans in cancer cells and tissues, but it remains to be systematically investigated if paucimannosylation is a significant cancer glycoepitope. This glycomics-centric study investigates the association of protein paucimannosylation with a wide range of human cancer types and subtypes i.e. brain, breast, liver, colorectal, prostate, ovarian and acute promyelocytic leukemia and matching non-cancerous cultured cells and tissues by mapping the distribution of paucimannosidic N-glycans using porous graphitised carbon liquid chromatography tandem mass spectrometry. This N-glycomics strategy was able to accurately determine the total level of paucimannosidic glycans within the N-glycome and map the relative abundance of the individual paucimannosidic species including M2, M2F, M3 and M3F. The total level of paucimannosidic N-glycans varied dramatically across the cancer types (4-35%, n = 3 for all cancers), even within cancer sub-types as shown for the variation across six breast cancer subtypes (4-13%), but were in general higher than the paucimannosidic levels in non-cancerous cells (0-3%). The core fucosylated M2F and M3F were the predominant paucimannosidic N-glycans identified across the studied cancers and clear subcellular-specific differences were observed by the different levels of paucimannosylation in various protein extracts from the same cells. Based on these preliminary correlation-type observations, we conclude that protein paucimannosylation represents significant, but non-uniform glycoepitopes of human cancers. These findings advance our understanding of the glyco-features expressed by human cancers and promote further cause-effect type studies of paucimannosylation in tumorigenesis and metastasis.

1Thaysen-Andersen, Venkatakrishnan, Loke, Laurini, Diestel, Parker, Packer. J Biol Chem 2015, 290(14), 8789.