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Mapping pH at Cancer Cell Surfaces.

Da Wei1, Donald M Engelman2, Yana K Reshetnyak1

  • 1Physics Department, University of Rhode Island, 2 Lippitt Rd, Kingston, RI, 02874, USA.

Molecular Imaging and Biology
|April 17, 2019
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel tool to measure cell surface pH, revealing that metastatic cancer cells exhibit lower pH due to higher glycolytic activity. This method links surface pH to cellular metabolism.

Keywords:
SNARF fluorescenceTumor acidityWarburg effectpH measurementspHLIP

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Area of Science:

  • Biophysics
  • Cell Biology
  • Cancer Research

Background:

  • Cell surface pH is a critical parameter influencing cellular functions.
  • Understanding cell surface pH dynamics is crucial for cancer diagnostics and therapeutics.
  • Existing methods lack the resolution to measure pH at the individual cell surface level.

Purpose of the Study:

  • To develop and validate a novel imaging tool for precise measurement of pH at the surface of individual cells.
  • To investigate the correlation between cell surface pH and cellular glycolytic activity.
  • To differentiate cancer cell types based on their surface pH profiles.

Main Methods:

  • Conjugation of SNARF pH-sensitive dye to a pH-Low Insertion Peptide (pHLIP®) for targeted binding to cellular membranes.
  • Simultaneous dual-wavelength (580 and 640 nm) imaging using a CCD camera and beam splitter.
  • Image ratio analysis to generate a pH map of individual cells within tumor spheroids.
  • Calculation of average cell surface pH and derivation of pH histograms.

Main Results:

  • The developed method successfully mapped the pH at the surface of individual cells in tumor spheroids.
  • Cell surface pH was found to be inversely correlated with cellular glycolytic activity, modulated by glucose and deoxy-glucose.
  • Metastatic cancer cells demonstrated a significantly lower surface pH compared to non-metastatic cells, indicating heightened glycolytic activity.

Conclusions:

  • The novel tool enables accurate measurement of cell surface pH.
  • Cell surface pH serves as a reliable indicator of cellular glycolytic activity.
  • This technique offers potential for distinguishing between metastatic and non-metastatic cancer cells based on metabolic profiles.