Journal
JOURNAL OF PROTEOME RESEARCH
Volume 14, Issue 6, Pages 2511-2519Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b00076
Keywords
MALDI-IMS; glioblastoma; xenografts; lipidomics; phosphatidic acid; diacylglycerol; docosahexaenoic acid; bone marrow-derived mesenchymal stem cells
Categories
Funding
- Cancer Prevention Research Institute of Texas (CPRIT)
- The University of Texas Medical Branch
- National Cancer Institute [CA115729, 1P50 CA127001]
- Broach Foundation for Brain Cancer Research
- Elias Family Fund
- National Brain Tumor Foundation
- Collaborative Ependymoma Research Network (CERN)
- The Gene Pennebaker Brain Cancer Fund
- The Sorenson Foundation
- The Brian McCulloch Fund
- Lincoln Memorial University
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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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