Visualization of sialidase activity in Mammalian tissues and cancer detection with a novel fluorescent sialidase substrate

PLoS One. 2014 Jan 10;9(1):e81941. doi: 10.1371/journal.pone.0081941. eCollection 2014.

Abstract

Sialidase removes sialic acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based sialic acid derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / enzymology
  • Brain / metabolism
  • Cell Line, Tumor
  • Enzyme Activation
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / toxicity
  • Humans
  • Hydrolysis
  • Male
  • Mammals
  • Mice
  • Molecular Imaging / methods*
  • Neoplasms / diagnosis
  • Neoplasms / metabolism
  • Neuraminidase / metabolism*
  • Rats
  • Substrate Specificity

Substances

  • Fluorescent Dyes
  • Neuraminidase

Grants and funding

This work was supported by Grant-in-Aid for Young Scientists (B) (KAKENHI; no. 24790080), The Sasakawa Scientific Research Grant from the Japan Science Society and The Naito Foundation Subsidy for Promotion of Specific Research Projects. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.