Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas

Cecile Riviere-Cazaux; Lucas P. Carlstrom; Karishma Rajani; Amanda Munoz-Casabella; Masum Rahman; Ali Gharibi-Loron; Desmond A. Brown; Kai J. Miller; Jaclyn J. White; Benjamin T. Himes; Ignacio Jusue-Torres; Samar Ikram; Seth C. Ransom; Renee Hirte; Ju Hee Oh; William F. Elmquist; Jann N. Sarkaria; Rachael A. Vaubel; Moses Rodriguez; Arthur E. Warrington; Sani H. Kizilbash; Terry C. Burns

doi:10.1038/s42003-023-05035-2

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas

Cecile Riviere-Cazaux, Lucas P. Carlstrom, Karishma Rajani, Amanda Munoz-Casabella, Masum Rahman, Ali Gharibi-Loron, Desmond A. Brown, Kai J. Miller, Jaclyn J. White, Benjamin T. Himes, Ignacio Jusue-Torres, Samar Ikram, Seth C. Ransom, Renee Hirte, Ju Hee Oh, William F. Elmquist, Jann N. Sarkaria, Rachael A. Vaubel, Moses Rodriguez, Arthur E. WarringtonSani H. Kizilbash, Terry C. Burns

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05–10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

Original language	English (US)
Article number	653
Journal	Communications biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05035-2
State	Published - Dec 2023

Bibliographical note

Funding Information:
We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS).

Funding Information:
We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS).

Publisher Copyright:
© 2023, The Author(s).

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.1038/s42003-023-05035-2

Find It

Find It at U of M Libraries

Cite this

Riviere-Cazaux, C., Carlstrom, L. P., Rajani, K., Munoz-Casabella, A., Rahman, M., Gharibi-Loron, A., Brown, D. A., Miller, K. J., White, J. J., Himes, B. T., Jusue-Torres, I., Ikram, S., Ransom, S. C., Hirte, R., Oh, J. H., Elmquist, W. F., Sarkaria, J. N., Vaubel, R. A., Rodriguez, M., ... Burns, T. C. (2023). Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas. Communications biology, 6(1), Article 653. https://doi.org/10.1038/s42003-023-05035-2

Riviere-Cazaux, C, Carlstrom, LP, Rajani, K, Munoz-Casabella, A, Rahman, M, Gharibi-Loron, A, Brown, DA, Miller, KJ, White, JJ, Himes, BT, Jusue-Torres, I, Ikram, S, Ransom, SC, Hirte, R, Oh, JH , Elmquist, WF, Sarkaria, JN, Vaubel, RA, Rodriguez, M, Warrington, AE, Kizilbash, SH & Burns, TC 2023, 'Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas', Communications biology, vol. 6, no. 1, 653. https://doi.org/10.1038/s42003-023-05035-2

@article{570161ddea9041ff916914ad58dbdad1,

title = "Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas",

abstract = "The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05–10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.",

author = "Cecile Riviere-Cazaux and Carlstrom, {Lucas P.} and Karishma Rajani and Amanda Munoz-Casabella and Masum Rahman and Ali Gharibi-Loron and Brown, {Desmond A.} and Miller, {Kai J.} and White, {Jaclyn J.} and Himes, {Benjamin T.} and Ignacio Jusue-Torres and Samar Ikram and Ransom, {Seth C.} and Renee Hirte and Oh, {Ju Hee} and Elmquist, {William F.} and Sarkaria, {Jann N.} and Vaubel, {Rachael A.} and Moses Rodriguez and Warrington, {Arthur E.} and Kizilbash, {Sani H.} and Burns, {Terry C.}",

note = "Funding Information: We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS). Funding Information: We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s42003-023-05035-2",

language = "English (US)",

volume = "6",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas

AU - Riviere-Cazaux, Cecile

AU - Carlstrom, Lucas P.

AU - Rajani, Karishma

AU - Munoz-Casabella, Amanda

AU - Rahman, Masum

AU - Gharibi-Loron, Ali

AU - Brown, Desmond A.

AU - Miller, Kai J.

AU - White, Jaclyn J.

AU - Himes, Benjamin T.

AU - Jusue-Torres, Ignacio

AU - Ikram, Samar

AU - Ransom, Seth C.

AU - Hirte, Renee

AU - Oh, Ju Hee

AU - Elmquist, William F.

AU - Sarkaria, Jann N.

AU - Vaubel, Rachael A.

AU - Rodriguez, Moses

AU - Warrington, Arthur E.

AU - Kizilbash, Sani H.

AU - Burns, Terry C.

N1 - Funding Information: We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS). Funding Information: We would like to thank each of our patients who selflessly participated in this study and without whom this work and any advancement in the field of neuro-oncology would not be possible. We also thank Elizabeth Oishi for regulatory support and the Mayo Clinic Neurosurgery Clinical Research team, and the Mayo neurosurgery operative staff for their invaluable support. CRC was supported by the National Institute of Health T32GM065841. TCB was supported by NINDS NRCDP K12, NINDS R61 NS122096, Mayo Clinic Center for Individualized Medicine and CCaTS award UL1TR002377, the American Brain Tumor Association, Brains Together for the Cure, Humor to fight the Tumor, and Lucius & Terrie McKelvey. Support was provided to TCB, SHK, AEW, and RAV through NCI R37CA276851. Support was also provided through NCI U54 CA210180 (JS). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05–10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

AB - The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05–10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

UR - http://www.scopus.com/inward/record.url?scp=85162859351&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85162859351&partnerID=8YFLogxK

U2 - 10.1038/s42003-023-05035-2

DO - 10.1038/s42003-023-05035-2

M3 - Article

C2 - 37340056

AN - SCOPUS:85162859351

SN - 2399-3642

VL - 6

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 653

ER -

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas

Abstract

Bibliographical note

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this