Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets. J Immunother Cancer 2020 Aug;8(2)
Date
08/11/2020Pubmed ID
32771993Pubmed Central ID
PMC7418848DOI
10.1136/jitc-2020-000915Scopus ID
2-s2.0-85089262124 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
BACKGROUND: Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.
METHODS: In this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed targeted MS assays, and applied these to cell lines and primary patient samples to refine the list of candidate tumor markers. Candidates of interest detected by MS on MM patient samples were further validated using flow cytometry (FCM).
RESULTS: We identified 696 MM cell surface N-glycoproteins by CSC, and developed 73 targeted MS detection assays. MS-based validation using primary specimens detected 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that were validated by FCM, confirming their expression on the cell surface of primary MM patient cells.
CONCLUSIONS: This MM surface N-glycoproteome will be a valuable resource in the development of biomarkers and therapeutics. Further, we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.
Author List
Oldham RAA, Faber ML, Keppel TR, Buchberger AR, Waas M, Hari P, Gundry RL, Medin JAAuthors
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of WisconsinJeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCell Line
Female
Humans
Immunotherapy
Male
Membrane Glycoproteins
