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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 R; Lang, Frederick and Nilsson, Carol L LU (2015) In Journal of Proteome Research 14(6). p.9-2511
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... (More)

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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published
keywords
Animals, Brain Neoplasms, Diglycerides, Docosahexaenoic Acids, Glioma, Heterografts, Humans, Male, Mass Spectrometry, Mice, Mice, Nude, Neoplastic Stem Cells, Phosphatidic Acids, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
Journal of Proteome Research
volume
14
issue
6
pages
9 pages
publisher
The American Chemical Society
external identifiers
  • scopus:84930607031
ISSN
1535-3893
DOI
10.1021/acs.jproteome.5b00076
language
English
LU publication?
no
id
62711502-2fb0-4610-8145-6322613a4360
date added to LUP
2017-05-16 10:23:57
date last changed
2017-11-14 09:56:25
@article{62711502-2fb0-4610-8145-6322613a4360,
  abstract     = {<p>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.</p>},
  author       = {Wildburger, Norelle C and Wood, Paul L and Gumin, Joy and Lichti, Cheryl F and Emmett, Mark R and Lang, Frederick and Nilsson, Carol L},
  issn         = {1535-3893},
  keyword      = {Animals,Brain Neoplasms,Diglycerides,Docosahexaenoic Acids,Glioma,Heterografts,Humans,Male,Mass Spectrometry,Mice,Mice, Nude,Neoplastic Stem Cells,Phosphatidic Acids,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {9--2511},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts},
  url          = {http://dx.doi.org/10.1021/acs.jproteome.5b00076},
  volume       = {14},
  year         = {2015},
}