ESI-MS/MS and MALDI-IMS localization reveal alterations in phosphatidic acid, diacylglycerol, and DHA in glioma stem cell xenografts

Norelle C. Wildburger, Paul L. Wood, Joy Gumin, Cheryl F. Lichti, Mark Emmett, Frederick F. Lang, Carol L. Nilsson

Research output: Contribution to journalArticle

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Abstract

Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studies have demonstrated the feasibility of harnessing the homing capacity of BM-hMSCs for targeted delivery of cancer therapeutics, it is now also evident, based on clinically relevant glioma stem cell (GSC) models of GBMs, that BM-hMSCs demonstrate variable tropism toward these tumors. In this study, we compared the lipid environment of GSC xenografts that attract BM-hMSCs (N = 9) with those that do not attract (N = 9) to identify lipid modalities that are conducive to homing of BM-hMSC to GBMs. We identified lipids directly from tissue by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) of lipid extracts. Several species of signaling lipids, including phosphatidic acid (PA 36:2, PA 40:5, PA 42:5, and PA 42:7) and diacylglycerol (DAG 34:0, DAG 34:1, DAG 36:1, DAG 38:4, DAG 38:6, and DAG 40:6), were lower in attracting xenografts. Molecular lipid images showed that PA (36:2), DAG (40:6), and docosahexaenoic acid (DHA) were decreased within tumor regions of attracting xenografts. Our results provide the first evidence for lipid signaling pathways and lipid-mediated tumor inflammatory responses in the homing of BM-hMSCs to GSC xenografts. Our studies provide new fundamental knowledge on the molecular correlates of the differential homing capacity of BM-hMSCs toward GSC xenografts.

Original languageEnglish (US)
Pages (from-to)2511-2519
Number of pages9
JournalJournal of Proteome Research
Volume14
Issue number6
DOIs
StatePublished - Jun 5 2015

Fingerprint

Phosphatidic Acids
Docosahexaenoic Acids
Diglycerides
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Stem cells
Heterografts
Glioma
Ionization
Mass spectrometry
Mesenchymal Stromal Cells
Desorption
Stem Cells
Bone Marrow
Lipids
Imaging techniques
Lasers
Bone
Tumors
Glioblastoma
Neoplasms

Keywords

  • bone marrow-derived mesenchymal stem cells
  • diacylglycerol
  • docosahexaenoic acid
  • glioblastoma
  • lipidomics
  • MALDI-IMS
  • phosphatidic acid
  • xenografts

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

ESI-MS/MS and MALDI-IMS localization reveal alterations in phosphatidic acid, diacylglycerol, and DHA in glioma stem cell xenografts. / Wildburger, Norelle C.; Wood, Paul L.; Gumin, Joy; Lichti, Cheryl F.; Emmett, Mark; Lang, Frederick F.; Nilsson, Carol L.

In: Journal of Proteome Research, Vol. 14, No. 6, 05.06.2015, p. 2511-2519.

Research output: Contribution to journalArticle

Wildburger, Norelle C. ; Wood, Paul L. ; Gumin, Joy ; Lichti, Cheryl F. ; Emmett, Mark ; Lang, Frederick F. ; Nilsson, Carol L. / ESI-MS/MS and MALDI-IMS localization reveal alterations in phosphatidic acid, diacylglycerol, and DHA in glioma stem cell xenografts. In: Journal of Proteome Research. 2015 ; Vol. 14, No. 6. pp. 2511-2519.
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AU - Wildburger, Norelle C.

AU - Wood, Paul L.

AU - Gumin, Joy

AU - Lichti, Cheryl F.

AU - Emmett, Mark

AU - Lang, Frederick F.

AU - Nilsson, Carol L.

PY - 2015/6/5

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N2 - Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studies have demonstrated the feasibility of harnessing the homing capacity of BM-hMSCs for targeted delivery of cancer therapeutics, it is now also evident, based on clinically relevant glioma stem cell (GSC) models of GBMs, that BM-hMSCs demonstrate variable tropism toward these tumors. In this study, we compared the lipid environment of GSC xenografts that attract BM-hMSCs (N = 9) with those that do not attract (N = 9) to identify lipid modalities that are conducive to homing of BM-hMSC to GBMs. We identified lipids directly from tissue by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) of lipid extracts. Several species of signaling lipids, including phosphatidic acid (PA 36:2, PA 40:5, PA 42:5, and PA 42:7) and diacylglycerol (DAG 34:0, DAG 34:1, DAG 36:1, DAG 38:4, DAG 38:6, and DAG 40:6), were lower in attracting xenografts. Molecular lipid images showed that PA (36:2), DAG (40:6), and docosahexaenoic acid (DHA) were decreased within tumor regions of attracting xenografts. Our results provide the first evidence for lipid signaling pathways and lipid-mediated tumor inflammatory responses in the homing of BM-hMSCs to GSC xenografts. Our studies provide new fundamental knowledge on the molecular correlates of the differential homing capacity of BM-hMSCs toward GSC xenografts.

AB - Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studies have demonstrated the feasibility of harnessing the homing capacity of BM-hMSCs for targeted delivery of cancer therapeutics, it is now also evident, based on clinically relevant glioma stem cell (GSC) models of GBMs, that BM-hMSCs demonstrate variable tropism toward these tumors. In this study, we compared the lipid environment of GSC xenografts that attract BM-hMSCs (N = 9) with those that do not attract (N = 9) to identify lipid modalities that are conducive to homing of BM-hMSC to GBMs. We identified lipids directly from tissue by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) of lipid extracts. Several species of signaling lipids, including phosphatidic acid (PA 36:2, PA 40:5, PA 42:5, and PA 42:7) and diacylglycerol (DAG 34:0, DAG 34:1, DAG 36:1, DAG 38:4, DAG 38:6, and DAG 40:6), were lower in attracting xenografts. Molecular lipid images showed that PA (36:2), DAG (40:6), and docosahexaenoic acid (DHA) were decreased within tumor regions of attracting xenografts. Our results provide the first evidence for lipid signaling pathways and lipid-mediated tumor inflammatory responses in the homing of BM-hMSCs to GSC xenografts. Our studies provide new fundamental knowledge on the molecular correlates of the differential homing capacity of BM-hMSCs toward GSC xenografts.

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KW - diacylglycerol

KW - docosahexaenoic acid

KW - glioblastoma

KW - lipidomics

KW - MALDI-IMS

KW - phosphatidic acid

KW - xenografts

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