Tracing Chemical Alterations in Cancer Cells and Tissues
(2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- Cancer is a leading cause of death worldwide, with approximately ten million people dying from the disease each year. In most cases, cancer metastasizes to distant organs and develops resistance to therapy, highlighting the need for novel biomarkers for early detection. This thesis investigates the role of lipid metabolism changes, particularly involving cholesterol and related lipid species, as early biomarkers for cancer detection and therapeutic resistance. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we explored tissue and cellular models to improve understanding of how spatial and molecular alterations in lipid profiles contribute to cancer progression and therapy adaptation.
At the tissue level, we examined... (More) - Cancer is a leading cause of death worldwide, with approximately ten million people dying from the disease each year. In most cases, cancer metastasizes to distant organs and develops resistance to therapy, highlighting the need for novel biomarkers for early detection. This thesis investigates the role of lipid metabolism changes, particularly involving cholesterol and related lipid species, as early biomarkers for cancer detection and therapeutic resistance. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we explored tissue and cellular models to improve understanding of how spatial and molecular alterations in lipid profiles contribute to cancer progression and therapy adaptation.
At the tissue level, we examined the alteration of cholesterol fidelity in mammary glands of mice, finding a significant increase in the fractional abundance of cholesterol fragment peaks (C27H45+) in cancerous tissues. This suggests that dysregulated cholesterol metabolism within the tumor can be traced via the molecular structure of cholesterol. In human glioblastoma multiforme (GBM), a highly aggressive brain cancer, we analyzed lipid distribution across different tumor regions and observed significant heterogeneity in cholesterol localization. These results indicate that cholesterol reprogramming is a key feature of tumor development, supporting uncontrolled growth, proliferation, and tumor heterogeneity.
At the cellular level, we investigated cisplatin-treated cancer cells, focusing on those that survived therapy. These cells exhibited a therapy-resistant phenotype, characterized by increased cell and nuclear size and the accumulation of lipid droplets. Multivariate analysis of ToF-SIMS data revealed distinct chemical profiles in lipid droplets compared to untreated cells, suggesting their role in chemotherapy resistance and cancer cell survival.
This thesis highlights the importance of lipid metabolism in cancer progression and its potential as a target for early detection and therapeutic intervention. By integrating high-resolution mass spectrometry, these insights may pave the way for developing diagnostic tools to detect cancer early and monitor treatment response more effectively. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/d5a3a3a9-3d29-4a69-8b33-8e6fac7b8dca
- author
- Manaprasertsak, Auraya LU
- supervisor
- opponent
-
- Dr. Jaouen, Klervia, Department of Geosciences and Environment, Observatory Midi Pyrénées in Toulouse, France
- organization
- publishing date
- 2025
- type
- Thesis
- publication status
- published
- subject
- keywords
- cancer, cholesterol, lipid, Time-of-flight secondary ion mass spectrometry, Mammary glands, glioblastoma multiforme (GBM), early detection
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2025:16
- pages
- 73 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Segerfalksalen, BMC A10, Sölvegatan 17 i Lund.
- defense date
- 2025-02-25 13:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-669-2
- language
- English
- LU publication?
- yes
- id
- d5a3a3a9-3d29-4a69-8b33-8e6fac7b8dca
- date added to LUP
- 2025-02-04 09:59:55
- date last changed
- 2025-04-04 15:08:59
@phdthesis{d5a3a3a9-3d29-4a69-8b33-8e6fac7b8dca,
abstract = {{Cancer is a leading cause of death worldwide, with approximately ten million people dying from the disease each year. In most cases, cancer metastasizes to distant organs and develops resistance to therapy, highlighting the need for novel biomarkers for early detection. This thesis investigates the role of lipid metabolism changes, particularly involving cholesterol and related lipid species, as early biomarkers for cancer detection and therapeutic resistance. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we explored tissue and cellular models to improve understanding of how spatial and molecular alterations in lipid profiles contribute to cancer progression and therapy adaptation.<br/>At the tissue level, we examined the alteration of cholesterol fidelity in mammary glands of mice, finding a significant increase in the fractional abundance of cholesterol fragment peaks (C27H45+) in cancerous tissues. This suggests that dysregulated cholesterol metabolism within the tumor can be traced via the molecular structure of cholesterol. In human glioblastoma multiforme (GBM), a highly aggressive brain cancer, we analyzed lipid distribution across different tumor regions and observed significant heterogeneity in cholesterol localization. These results indicate that cholesterol reprogramming is a key feature of tumor development, supporting uncontrolled growth, proliferation, and tumor heterogeneity.<br/>At the cellular level, we investigated cisplatin-treated cancer cells, focusing on those that survived therapy. These cells exhibited a therapy-resistant phenotype, characterized by increased cell and nuclear size and the accumulation of lipid droplets. Multivariate analysis of ToF-SIMS data revealed distinct chemical profiles in lipid droplets compared to untreated cells, suggesting their role in chemotherapy resistance and cancer cell survival.<br/>This thesis highlights the importance of lipid metabolism in cancer progression and its potential as a target for early detection and therapeutic intervention. By integrating high-resolution mass spectrometry, these insights may pave the way for developing diagnostic tools to detect cancer early and monitor treatment response more effectively.}},
author = {{Manaprasertsak, Auraya}},
isbn = {{978-91-8021-669-2}},
issn = {{1652-8220}},
keywords = {{cancer; cholesterol; lipid; Time-of-flight secondary ion mass spectrometry; Mammary glands; glioblastoma multiforme (GBM); early detection}},
language = {{eng}},
number = {{2025:16}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Tracing Chemical Alterations in Cancer Cells and Tissues}},
url = {{https://lup.lub.lu.se/search/files/207722386/e-nailing_ex_Auraya.pdf}},
year = {{2025}},
}