Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1

  • ACS Cent Sci. 2018 Aug 22;4(8):1045-1055. doi: 10.1021/acscentsci.8b00313.
Chelsea Anorma  1 ,  Jamila Hedhli  2  3 ,  Thomas E Bearrood  1 ,  Nicholas W Pino  1 ,  Sarah H Gardner  1 ,  Hiroshi Inaba  1 ,  Pamela Zhang  1 ,  Yanfen Li  2 ,  Daven Feng  1 ,  Sara E Dibrell  1 ,  Kristopher A Kilian  2  4 ,  Lawrence W Dobrucki  2  3 ,  Timothy M Fan  5 ,  Jefferson Chan  1  1  3
Affiliations
  • 1. Department of Chemistry and Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United States.
  • 2. Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Avenue, Urbana, Illinois 61801, United States.
  • 3. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Mathews Avenue, Urbana, Illinois 61801, United States.
  • 4. School of Materials Science and Engineering, School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • 5. Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, Illinois 61801, United States.
PMID: 30159402 DOI: 10.1021/acscentsci.8b00313
Abstract

Cancer Stem Cells (CSCs) are progenitor cells that contribute to treatment-resistant phenotypes during relapse. CSCs exist in specific tissue microenvironments that cell cultures and more complex models cannot mimic. Therefore, the development of new approaches that can detect CSCs and report on specific properties (e.g., stem cell plasticity) in their native environment have profound implications for studying CSC biology. Herein, we present AlDeSense, a turn-on fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching nonresponsive reagent. Although ALDH1A1 contributes to the detoxification of reactive aldehydes, it is also associated with stemness and is highly elevated in CSCs. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Moreover, we established that AlDeSense is selective against a panel of common ALDH isoforms and exhibits exquisite chemostability against a collection of biologically relevant species. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, we demonstrate that cells exhibiting high AlDeSense signal intensity have properties of CSCs. Using these probes in tandem, we have identified CSCs at the cellular level via flow cytometry and confocal imaging, as well as monitored their states in animal models.

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