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Alterations of the chemical profile of cholesterol in cancer tissue as traced with ToF-SIMS

Manaprasertsak, Auraya LU ; Kazi, Julhash U. LU orcid ; Hagerling, Catharina LU ; Pienta, Kenneth J. LU ; Malmberg, Per LU and Hammarlund, Emma U. LU (2024) In Analyst 21. p.5344-5352
Abstract

Cancer has become one of the leading causes of death, with approximately ten million people worldwide dying from cancer each year. In most cases, cancer spreads to remote organs and develops a resistance to therapy. To reduce the deadly impact of cancer, novel targets for markers for early detection are necessary. Given the notable influence of rapid chemical turnover on isotope effects, the heightened turnover rate of cholesterol in cancer offers a promising way for investigation. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) offers a valuable tool of tracking cholesterol dynamics. Consequently, we employed ToF-SIMS to assess cholesterol alterations, aiming to uncover potential diagnostic vulnerabilities stemming from... (More)

Cancer has become one of the leading causes of death, with approximately ten million people worldwide dying from cancer each year. In most cases, cancer spreads to remote organs and develops a resistance to therapy. To reduce the deadly impact of cancer, novel targets for markers for early detection are necessary. Given the notable influence of rapid chemical turnover on isotope effects, the heightened turnover rate of cholesterol in cancer offers a promising way for investigation. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) offers a valuable tool of tracking cholesterol dynamics. Consequently, we employed ToF-SIMS to assess cholesterol alterations, aiming to uncover potential diagnostic vulnerabilities stemming from heightened cholesterol synthesis. Our study explored the chemical profile of cholesterol influenced by cancer cell metabolism using mammary glands from mice, both with and without cancer. Results revealed a significant increase in the fractional abundance of fragment cholesterol peaks (C27H45+) in cancerous tissues, indicating dysregulated cholesterol metabolism within cancer cells. This suggests potential structural weaknesses or incomplete synthesis. Further investigation into carbon isotope incorporation suggests that the isotopic patterns might be due to the integration of heavier carbon isotopes, although these patterns could be affected by other isotopic influences. Nevertheless, understanding isotope effect of cholesterol profiles have the potential to advance our understanding of cancer biology and improve diagnostic approaches.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Analyst
volume
21
article number
5344
pages
5344 - 5352
publisher
Royal Society of Chemistry
external identifiers
  • pmid:39329417
  • scopus:85205895951
ISSN
0003-2654
DOI
10.1039/d4an01050g
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Royal Society of Chemistry.
id
8d5f2318-ab3e-4411-9872-1a0384fc430e
date added to LUP
2025-01-14 15:57:48
date last changed
2025-07-02 06:06:50
@article{8d5f2318-ab3e-4411-9872-1a0384fc430e,
  abstract     = {{<p>Cancer has become one of the leading causes of death, with approximately ten million people worldwide dying from cancer each year. In most cases, cancer spreads to remote organs and develops a resistance to therapy. To reduce the deadly impact of cancer, novel targets for markers for early detection are necessary. Given the notable influence of rapid chemical turnover on isotope effects, the heightened turnover rate of cholesterol in cancer offers a promising way for investigation. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) offers a valuable tool of tracking cholesterol dynamics. Consequently, we employed ToF-SIMS to assess cholesterol alterations, aiming to uncover potential diagnostic vulnerabilities stemming from heightened cholesterol synthesis. Our study explored the chemical profile of cholesterol influenced by cancer cell metabolism using mammary glands from mice, both with and without cancer. Results revealed a significant increase in the fractional abundance of fragment cholesterol peaks (C<sub>27</sub>H<sub>45</sub><sup>+</sup>) in cancerous tissues, indicating dysregulated cholesterol metabolism within cancer cells. This suggests potential structural weaknesses or incomplete synthesis. Further investigation into carbon isotope incorporation suggests that the isotopic patterns might be due to the integration of heavier carbon isotopes, although these patterns could be affected by other isotopic influences. Nevertheless, understanding isotope effect of cholesterol profiles have the potential to advance our understanding of cancer biology and improve diagnostic approaches.</p>}},
  author       = {{Manaprasertsak, Auraya and Kazi, Julhash U. and Hagerling, Catharina and Pienta, Kenneth J. and Malmberg, Per and Hammarlund, Emma U.}},
  issn         = {{0003-2654}},
  language     = {{eng}},
  pages        = {{5344--5352}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Analyst}},
  title        = {{Alterations of the chemical profile of cholesterol in cancer tissue as traced with ToF-SIMS}},
  url          = {{http://dx.doi.org/10.1039/d4an01050g}},
  doi          = {{10.1039/d4an01050g}},
  volume       = {{21}},
  year         = {{2024}},
}