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Cell types or cell states? An investigation of adrenergic and mesenchymal cell phenotypes in neuroblastoma

Bukkuri, Anuraag LU ; Andersson, Stina LU ; Mazariegos, Marina S. LU orcid ; Brown, Joel S. ; Hammarlund, Emma U. LU and Mohlin, Sofie LU orcid (2024) In iScience 27(12).
Abstract

Neuroblastoma exhibits two cellular phenotypes: therapy-sensitive adrenergic (ADRN) and therapy-resistant mesenchymal (MES). To understand treatment response, it is important to elucidate how these phenotypes impact the dynamics of cancer cell populations and whether they represent distinct cell types or dynamic cell states. Here, we use an integrated experimental and mathematical modeling approach. We experimentally measure the fractions of ADRN and MES phenotypes under baseline (untreated) conditions and under repeated treatment cycles. We develop evolutionary game theoretic models predicting how the populations would respond if ADRN and MES phenotypes (1) are distinct cell types or (2) represent dynamic cell states and fit these... (More)

Neuroblastoma exhibits two cellular phenotypes: therapy-sensitive adrenergic (ADRN) and therapy-resistant mesenchymal (MES). To understand treatment response, it is important to elucidate how these phenotypes impact the dynamics of cancer cell populations and whether they represent distinct cell types or dynamic cell states. Here, we use an integrated experimental and mathematical modeling approach. We experimentally measure the fractions of ADRN and MES phenotypes under baseline (untreated) conditions and under repeated treatment cycles. We develop evolutionary game theoretic models predicting how the populations would respond if ADRN and MES phenotypes (1) are distinct cell types or (2) represent dynamic cell states and fit these models to the experimental data. We find that, although cells may undergo an ADRN to MES phenotypic switch under treatment, the best-fit model sees ADRN and MES as distinct cell types. Differential proliferation and survival of these two cell types, and not cell-state switching, drive therapeutic response.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biological sciences, Neuroscience
in
iScience
volume
27
issue
12
article number
111433
publisher
Elsevier
external identifiers
  • pmid:39687008
  • scopus:85210378195
ISSN
2589-0042
DOI
10.1016/j.isci.2024.111433
language
English
LU publication?
yes
id
d4d882e9-7346-45a8-a30a-ec2759389438
date added to LUP
2025-01-07 14:46:36
date last changed
2025-06-11 03:19:56
@article{d4d882e9-7346-45a8-a30a-ec2759389438,
  abstract     = {{<p>Neuroblastoma exhibits two cellular phenotypes: therapy-sensitive adrenergic (ADRN) and therapy-resistant mesenchymal (MES). To understand treatment response, it is important to elucidate how these phenotypes impact the dynamics of cancer cell populations and whether they represent distinct cell types or dynamic cell states. Here, we use an integrated experimental and mathematical modeling approach. We experimentally measure the fractions of ADRN and MES phenotypes under baseline (untreated) conditions and under repeated treatment cycles. We develop evolutionary game theoretic models predicting how the populations would respond if ADRN and MES phenotypes (1) are distinct cell types or (2) represent dynamic cell states and fit these models to the experimental data. We find that, although cells may undergo an ADRN to MES phenotypic switch under treatment, the best-fit model sees ADRN and MES as distinct cell types. Differential proliferation and survival of these two cell types, and not cell-state switching, drive therapeutic response.</p>}},
  author       = {{Bukkuri, Anuraag and Andersson, Stina and Mazariegos, Marina S. and Brown, Joel S. and Hammarlund, Emma U. and Mohlin, Sofie}},
  issn         = {{2589-0042}},
  keywords     = {{Biological sciences; Neuroscience}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Cell types or cell states? An investigation of adrenergic and mesenchymal cell phenotypes in neuroblastoma}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2024.111433}},
  doi          = {{10.1016/j.isci.2024.111433}},
  volume       = {{27}},
  year         = {{2024}},
}