Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206)

Kathrin Stavenhagen, Lisa C. Laan, Chao Gao, Akul Y. Mehta, Jamie Heimburg-Molinaro, Jonathan N. Glickman, Irma van Die, Richard D. Cummings*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied. Here we used the murine MR CTLD4–7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition. We probed 16 different cancer and control tissues using the MR-Fc, and observed cell- and tissue-specific binding with varying intensity. All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located. We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry. To characterize the fine specificity of the MR for glycans, we screened a panel of glycan microarrays. Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested. As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis. All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results. Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
Original languageEnglish
Pages (from-to)5569-5585
Number of pages17
JournalCellular and Molecular Life Sciences
Issue number14
Early online date2021
Publication statusPublished - Jul 2021

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