ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts
(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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- author
- Wildburger, Norelle C ; Wood, Paul L ; Gumin, Joy ; Lichti, Cheryl F ; Emmett, Mark R ; Lang, Frederick and Nilsson, Carol L LU
- publishing date
- 2015-06-05
- type
- Contribution to journal
- publication status
- 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 (ACS)
- external identifiers
-
- pmid:25880480
- 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
- 2024-03-17 12:07:26
@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}},
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}},
language = {{eng}},
month = {{06}},
number = {{6}},
pages = {{9--2511}},
publisher = {{The American Chemical Society (ACS)}},
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}},
doi = {{10.1021/acs.jproteome.5b00076}},
volume = {{14}},
year = {{2015}},
}