Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models

被引:118
作者
Chughtai, Kamila [1 ]
Jiang, Lu [2 ]
Greenwood, Tiffany R. [2 ]
Glunde, Kristine [2 ,3 ]
Heeren, Ron M. A. [1 ,4 ]
机构
[1] FOM Inst AMOLF, NL-1098 XG Amsterdam, Netherlands
[2] Johns Hopkins Univ, Vivo Cellular & Mol Imaging Ctr Program, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Canc Imaging Res, Baltimore, MD 21205 USA
[4] Netherlands Prote Ctr, NL-3508 TB Utrecht, Netherlands
基金
美国国家卫生研究院;
关键词
multimodal imaging; phospholipids; matrix-assisted laser desorption/ionization; mass spectrometry; FATTY-ACID-METABOLISM; OVARIAN-CANCER; LYSOPHOSPHATIDIC ACID; CERAMIDE; 1-PHOSPHATE; LIPID ANALYSIS; MOUSE MODEL; BRAIN; HYPOXIA; TISSUE; PHOSPHOLIPIDS;
D O I
10.1194/jlr.M027961
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis. Recent developments in MALDI mass spectrometry imaging (MSI) enable rapid and specific detection of lipids directly from thin tissue sections. In this study, we performed multimodal imaging of acylcarnitines, phosphatidylcholines (PC), a lysophosphatidylcholine (LPC), and a sphingomyelin (SM) from different microenvironments of breast tumor xenograft models, which carried tdTomato red fluorescent protein as a hypoxia-response element-driven reporter gene. The MSI molecular lipid images revealed spatially heterogeneous lipid distributions within tumor tissue. Four of the most-abundant lipid species, namely PC(16:0/16:0), PC(16:0/18:1), PC(18:1/18:1), and PC(18: 0/18: 1), were localized in viable tumor regions, whereas LPC(16:0/0:0) was detected in necrotic tumor regions. We identified a heterogeneous distribution of palmitoylcarnitine, stearoylcarnitine, PC(16:0/22:1), and SM(d18:1/16:0) sodium adduct, which colocalized primarily with hypoxic tumor regions.(jlr) For the first time, we have applied a multimodal imaging approach that has combined optical imaging and MALDI-MSI with ion mobility separation to spatially localize and structurally identify acylcarnitines and a variety of lipid species present in breast tumor xenograft models.-Chughtai, K., L. Jiang, T. R. Greenwood, K. Glunde, and R. M. A. Heeren. Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models. J. Lipid Res. 2013. 54: 333-344.
引用
收藏
页码:333 / 344
页数:12
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