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.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Wildburger NC,Wood PL,Gumin J,Lichti CF,Emmett MR,Lang FF,Nilsson CLdoi
10.1021/acs.jproteome.5b00076subject
Has Abstractpub_date
2015-06-05 00:00:00pages
2511-9issue
6eissn
1535-3893issn
1535-3907journal_volume
14pub_type
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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更新日期：2004-09-01 00:00:00
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更新日期：2013-01-04 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
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更新日期：2011-08-05 00:00:00
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doi：10.1021/acs.jproteome.0c00685
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