2021-01-28T12:08:29 n8324

Isomer-resolved lipidomics for analysis of human prostate tumours and cancer cell lines

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Abstract

Fatty acid (FA) modifications, such as enzymatic desaturation and elongation, have long been thought to involve sequential and highly specific enzyme-substrate interactions, which result in canonical products that are well-defined in their chain lengths, degree of unsaturation and double bond positions. These products act as a supply of building blocks for the synthesis of complex lipids supporting a symphony of lipid signals and membrane macrostructure.

Recently, it was brought to light that differences in substrate availability due to enzyme inhibition can activate alternative pathways in a range of cancers, potentially altering the total species repertoire of FA metabolism. We have used isomer-resolved lipidomics to analyse human prostate tumours and cancer cell lines and that reveal, for the first-time, the full extent of metabolic plasticity in cancer.

Assigning the double bond position(s) in simple and complex lipids allows mapping of fatty acid desaturation and elongation via hitherto apocryphal metabolic pathways that generate FAs with unusual sites of unsaturation. Downstream utilisation of these FAs is demonstrated by their incorporation into complex structural lipids. The unsaturation profiles of different phospholipids reveal substantive structural variation between classes that will, necessarily, modulate lipid-centred biological processes in cancer cells including membrane fluidity and signal transduction.

Geographical area of data collection

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Direct infusion OzID and MSMS experiments: Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology, 2 George St, Brisbane, QLD 4000, Australia.
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Biological and patient samples/data: Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Princess Alexandra Hospital, Translational Research Institute, Brisbane 4000, Australia.
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MALDI-MSI-OzID: M4I, The Maastricht MultiModal Molecular Imaging Institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, MD, Maastricht, The Netherlands.

Publications

Paine, Martin, Poad, Berwyck, Eijkel, Gert, Marshall, David, Blanksby, Stephen, Heeren, Ron, & Ellis, Shane (2018) Mass spectrometry imaging with isomeric resolution enabled by ozone-induced dissociation. Angewandte Chemie (International Edition), 57(33), pp. 10524-10530. https://eprints.qut.edu.au/120319/
Poad, Berwyck, Marshall, David, Harazim, Eva, Gupta, Raj, Narreddula, Venkateswara Reddy, Young, Reuben, Duchoslav, Eva, Campbell, J., Broadbent, James, Cvacka, Josef, Mitchell, Todd, & Blanksby, Stephen (2019) Combining charge-switch derivatization with ozone-induced dissociation for fatty acid analysis. Journal of the American Society for Mass Spectrometry, 30(10), pp. 2135-2143. https://eprints.qut.edu.au/131340/
Tousignant, Kaylyn D, Rockstroh, Anja, Poad, Berwyck L J, Talebi, Ali, Young, Reuben S E, Taherian Fard, Atefeh, Gupta, Rajesh, Zang, Tuo, Wang, Chenwei, Lehman, Melanie L, Swinnen, Johan V, Blanksby, Stephen J, Nelson, Colleen C, & Sadowski, Martin C (2020) Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer. Cancer & Metabolism, 8, Article number: 11. https://eprints.qut.edu.au/202211/
Marshall, David, Criscuolo, Angela, Young, Reuben, Poad, Berwyck, Zeller, Martin, Reid, Gavin, Mitchell, Todd, & Blanksby, Stephen (2019) Mapping unsaturation in human plasma lipids by data-independent ozone-induced dissociation. Journal of the American Society for Mass Spectrometry, 30(9), pp. 1621-1630. https://eprints.qut.edu.au/130909/

Research areas

Fatty acids
Tissue imaging
Cell lines
siRNA
Isomer-resolved lipidomics
Lipids
Double bond isomers
Biochemistry
Prostate cancer
mRNA

Cite this collection

Young, Reuben; Bowman, Andrew; Williams, Elizabeth; Tousignant, Kaylyn; Bidgood, Charles; Narreddula, Venkateswara; Gupta, Rajesh; Marshall, David; Poad, Berwyck; Nelson, Colleen; Ellis, Shane; Heeren, Ron; Sadowski, Martin; Blanksby, Stephen (2020): Isomer-resolved lipidomics for analysis of human prostate tumours and cancer cell lines . Queensland University of Technology. (Dataset) https://doi.org/10.25912/5eddf867b9aee

Partner institution

Masstricht MultiModal Molecular Imaging Institute (M4I) https://www.maastrichtuniversity.nl/research/m4i-division-imaging-mass-spectrometry

Licence


Creative Commons Attribution-NonCommercial-Share Alike 4.0 (CC-BY-NC-SA)
http://creativecommons.org/licenses/by-nc-sa/4.0/

Copyright

© Reuben S. E. Young, 2020.

Dates of data collection

From 2018-02-12 to 2020-06-01

Connections

Has association with
Berwyck Poad  (Researcher)
Colleen Nelson  (Researcher)
David Marshall  (Researcher)
Elizabeth Williams  (Researcher)
Rajesh Gupta  (Researcher)
Reuben Young  (Researcher)
Venkateswara Narredula  (Researcher)
Has chief investigator
Stephen Blanksby  (Researcher)

Contacts

Name: Mr Reuben Young

Other

Date record created:
2020-06-05T15:44:01
Date record modified:
2021-01-28T12:08:29
Record status:
Published - Open Access