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

Chelsea Anorma, Jamila Hedhli, Thomas E. Bearrood, Nicholas W. Pino, Sarah H. Gardner, Hiroshi Inaba, Pamela Zhang, Yanfen Li, Daven Feng, Sara E. Dibrell, Kristopher A. Kilian, Wawrzyniec Dobrucki, Timothy M Fan, Jefferson Kar Fai Chan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1045-1055
Number of pages11
JournalACS Central Science
Volume4
Issue number8
DOIs
StatePublished - Aug 22 2018

Fingerprint

Aldehyde Dehydrogenase
Stem cells
Aldehydes
Fluorescent Dyes
Plasticity
Protein Isoforms
Cytology
Detoxification
Flow cytometry
Oxidoreductases
Cell culture
Antibodies
Assays
Animals
Tissue
Imaging techniques

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1. / Anorma, Chelsea; Hedhli, Jamila; Bearrood, Thomas E.; Pino, Nicholas W.; Gardner, Sarah H.; Inaba, Hiroshi; Zhang, Pamela; Li, Yanfen; Feng, Daven; Dibrell, Sara E.; Kilian, Kristopher A.; Dobrucki, Wawrzyniec; Fan, Timothy M; Chan, Jefferson Kar Fai.

In: ACS Central Science, Vol. 4, No. 8, 22.08.2018, p. 1045-1055.

Research output: Contribution to journalArticle

Anorma, C, Hedhli, J, Bearrood, TE, Pino, NW, Gardner, SH, Inaba, H, Zhang, P, Li, Y, Feng, D, Dibrell, SE, Kilian, KA, Dobrucki, W, Fan, TM & Chan, JKF 2018, 'Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1', ACS Central Science, vol. 4, no. 8, pp. 1045-1055. https://doi.org/10.1021/acscentsci.8b00313
Anorma, Chelsea ; Hedhli, Jamila ; Bearrood, Thomas E. ; Pino, Nicholas W. ; Gardner, Sarah H. ; Inaba, Hiroshi ; Zhang, Pamela ; Li, Yanfen ; Feng, Daven ; Dibrell, Sara E. ; Kilian, Kristopher A. ; Dobrucki, Wawrzyniec ; Fan, Timothy M ; Chan, Jefferson Kar Fai. / Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1. In: ACS Central Science. 2018 ; Vol. 4, No. 8. pp. 1045-1055.
@article{53ec14bc8b754f1f8643ef3fac10c9ac,
title = "Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1",
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.",
author = "Chelsea Anorma and Jamila Hedhli and Bearrood, {Thomas E.} and Pino, {Nicholas W.} and Gardner, {Sarah H.} and Hiroshi Inaba and Pamela Zhang and Yanfen Li and Daven Feng and Dibrell, {Sara E.} and Kilian, {Kristopher A.} and Wawrzyniec Dobrucki and Fan, {Timothy M} and Chan, {Jefferson Kar Fai}",
year = "2018",
month = "8",
day = "22",
doi = "10.1021/acscentsci.8b00313",
language = "English (US)",
volume = "4",
pages = "1045--1055",
journal = "ACS Central Science",
issn = "2374-7943",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1

AU - Anorma, Chelsea

AU - Hedhli, Jamila

AU - Bearrood, Thomas E.

AU - Pino, Nicholas W.

AU - Gardner, Sarah H.

AU - Inaba, Hiroshi

AU - Zhang, Pamela

AU - Li, Yanfen

AU - Feng, Daven

AU - Dibrell, Sara E.

AU - Kilian, Kristopher A.

AU - Dobrucki, Wawrzyniec

AU - Fan, Timothy M

AU - Chan, Jefferson Kar Fai

PY - 2018/8/22

Y1 - 2018/8/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85051986855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051986855&partnerID=8YFLogxK

U2 - 10.1021/acscentsci.8b00313

DO - 10.1021/acscentsci.8b00313

M3 - Article

AN - SCOPUS:85051986855

VL - 4

SP - 1045

EP - 1055

JO - ACS Central Science

JF - ACS Central Science

SN - 2374-7943

IS - 8

ER -