TY - JOUR
T1 - MALDI-MSI of lipids in a model of breast cancer brain metastasis provides a surrogate measure of ischemia/hypoxia
AU - Roux, Aurelie
AU - Winnard, Paul T.
AU - Van Voss, Marise Heerma
AU - Muller, Ludovic
AU - Jackson, Shelley N.
AU - Hoffer, Barry
AU - Woods, Amina S.
AU - Raman, Venu
N1 - Funding Information:
This research was supported in part by the Intramural Research Program of the National Institute on Drug Abuse, NIH. Venu Raman acknowledges support from Grant 1RO1CA207208.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/11
Y1 - 2023/11
N2 - Breast cancer brain metastasis (BCBM) has an incidence of 10–30%. It is incurable and the biological mechanisms that promote its progression remain largely undefined. Consequently, to gain insights into BCBM processes, we have developed a spontaneous mouse model of BCBM and in this study found a 20% penetrance of macro-metastatic brain lesion formation. Considering that lipid metabolism is indispensable to metastatic progression, our goal was the mapping of lipid distributions throughout the metastatic regions of the brain. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of lipids revealed that, relative to surrounding brain tissue, seven long-chain (13–21 carbons long) fatty acylcarnitines, as well as two phosphatidylcholines, two phosphatidylinositols two diacylglycerols, a long-chain phosphatidylethanolamine, and a long-chain sphingomyelin were highly concentrated in the metastatic brain lesion In broad terms, lipids known to be enriched in brain tissues, such as very long-chain (≥ 22 carbons in length) polyunsaturated fatty acid of phosphatidylcholines, phosphatidylethanolamine, sphingomyelins, sulfatides, phosphatidylinositol phosphates, and galactosylceramides, were not found or only found in trace amounts in the metastatic lesion and instead consistently detected in surrounding brain tissues. The data, from this mouse model, highlights an accumulation of fatty acylcarnitines as possible biological makers of a chaotic inefficient vasculature within the metastasis, resulting in relatively inadequate blood flow and disruption of fatty acid β-oxidation due to ischemia/hypoxia.
AB - Breast cancer brain metastasis (BCBM) has an incidence of 10–30%. It is incurable and the biological mechanisms that promote its progression remain largely undefined. Consequently, to gain insights into BCBM processes, we have developed a spontaneous mouse model of BCBM and in this study found a 20% penetrance of macro-metastatic brain lesion formation. Considering that lipid metabolism is indispensable to metastatic progression, our goal was the mapping of lipid distributions throughout the metastatic regions of the brain. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of lipids revealed that, relative to surrounding brain tissue, seven long-chain (13–21 carbons long) fatty acylcarnitines, as well as two phosphatidylcholines, two phosphatidylinositols two diacylglycerols, a long-chain phosphatidylethanolamine, and a long-chain sphingomyelin were highly concentrated in the metastatic brain lesion In broad terms, lipids known to be enriched in brain tissues, such as very long-chain (≥ 22 carbons in length) polyunsaturated fatty acid of phosphatidylcholines, phosphatidylethanolamine, sphingomyelins, sulfatides, phosphatidylinositol phosphates, and galactosylceramides, were not found or only found in trace amounts in the metastatic lesion and instead consistently detected in surrounding brain tissues. The data, from this mouse model, highlights an accumulation of fatty acylcarnitines as possible biological makers of a chaotic inefficient vasculature within the metastasis, resulting in relatively inadequate blood flow and disruption of fatty acid β-oxidation due to ischemia/hypoxia.
KW - Acylcarnitines
KW - Brain metastasis
KW - Breast cancer
KW - Lipid distributions
KW - MALDI-MSI
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U2 - 10.1007/s11010-023-04685-4
DO - 10.1007/s11010-023-04685-4
M3 - Article
C2 - 36884151
AN - SCOPUS:85149480672
SN - 0300-8177
VL - 478
SP - 2567
EP - 2580
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 11
ER -