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A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells

Summary

This research developed a new tool for detecting cancer cells by identifying specific sugar molecules that are present on cancer cells but rare on healthy cells. The tool is based on a protein derived from mushrooms that can specifically bind to these cancer-associated sugar patterns. Impacts on everyday life: – Provides a new potential method for detecting and diagnosing various types of cancer – Could help doctors better distinguish between cancerous and healthy tissue during diagnosis – May lead to more accurate cancer screening tests – Could help monitor cancer treatment effectiveness – May contribute to the development of new targeted cancer therapies

Background

Changes in cell surface glycosylation are associated with chronic diseases and cancer, with certain oligosaccharide epitopes being linked to cancer progression. Among these, truncated glycans with terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues are rare on healthy tissues but present in cancer. While lectins from unconventional sources like fungi can bind specifically to such epitopes, their availability can be challenging.

Objective

To produce and characterize a recombinant form of the GlcNAc-binding lectin from the fungus Psathyrella velutina (PVL) and evaluate its ability to specifically bind to and detect GlcNAc-terminated glycans on cancer cells and tissues.

Results

rPVL showed strong specificity for terminal GlcNAc residues with micromolar affinity for GlcNAcβ1-3Gal epitopes and biantennary N-glycans. Crystal structure analysis revealed the structural basis for this specificity. The lectin bound strongly to various cancer cell lines and showed specific labeling of cancer tissues with weak or no labeling of healthy tissues, except for stomach glands. Analysis confirmed higher amounts of GlcNAc present on cancer cells. Clear delineation was observed between cancer regions and surrounding healthy tissues in lung, breast and colon carcinomas.

Conclusion

rPVL is an effective tool for labeling agalacto-glycans in cancer and other diseases. The lectin shows promise as a diagnostic tool for detecting altered glycosylation patterns in various cancers, particularly non-small cell lung cancers, breast carcinomas, and colon carcinomas. Its specific binding properties make it useful for distinguishing between cancer and healthy tissues.
  • Published in:PLoS One,
  • Study Type:Laboratory Research,
  • Source: 10.1371/journal.pone.0128190
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