Liquid chromatography mass spectrometry for quantifying plasma lysophospholipids: Potential biomarkers for cancer diagnosis

被引:87
作者
Murph, Mandi
Tanaka, Tamotsu
Pang, Jihai
Felix, Edward
Liu, Shuying
Trost, Rosanne
Godwin, Andrew K.
Newman, Robert
Mills, Gordon
机构
[1] Univ Texas Houston, MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA
[2] Univ Texas Houston, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA
[3] Fukuyama Univ, Dept Appl Biol Sci, Fukuyama, Hiroshima, Japan
[4] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA
来源
LIPIDOMICS AND BIOACTIVE LIPIDS: SPECIALIZED ANALYTICAL METHODS AND LIPIDS IN DISEASE | 2007年 / 433卷
关键词
D O I
10.1016/S0076-6879(07)33001-2
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Cancer is a complex disease with many genetic and epigenetic aberrations that result in development of tumorigenic phenotypes. While many factors contribute to the etiology of cancer, emerging data implicate lysophospholipids acting through specific cell-surface, and potentially intracellular, receptors in acquiring the transformed phenotype propagated during disease. Lysophospholipids bind to and activate specific cell-surface G protein-coupled receptors (GPCRs) that initiate cell growth, proliferation, and survival pathways, and show altered expression in cancer cells. In addition, a number of enzymes that increase lysophospholipid production are elevated in particular cell lineages and cancer patients' cells, whereas in a subset of patients, the enzymes degrading lysophospholipids are decreased. Thus, ideal conditions are established to increase lysophospholipids in the tumor microenvironment. Indeed, ascites from ovarian cancer patients, which reflects both the tumor environment and a tumor-conditioned media, exhibits markedly elevated levels of specific lysophospholipids as well as one of the enzymes involved in production of lysophospholipids: autotaxin (ATX). The a potential sources of lysophospholipids in the tumor microenvironment include tumor cells and stroma, such as mesothelial cells, as well as inflammatory cells and platelets activated by the proinflammatory tumor environment. If lysophospholipids diffuse from the tumor microenvironment into the bloodstream and persist, they have the potential to serve as early diagnostic markers as well as potential monitors of tumor response to therapy. Many scientific and technical challenges need to be resolved to determine whether lysophospholipids or the enzymes producing lysophospholipids alone or in combination with other markers have the potential to contribute to early diagnosis. Breast cancer is the most frequently diagnosed cancer among women. Mammography is associated with morbidity and has a high false positive and false negative rate. Thus, there is a critical need for biomarkers that can contribute to a reduced false positive and false negative diagnoses, and to identify, stage, and/or predict prognosis of this disease to improve patient management. Here we describe a technical approach that can be applied to human blood plasma to measure the concentration of growth factor-like lysophospholipids contained in circulation. Using liquid chromatography mass spectrometry (LC/MS/MS), we quantified the amount of lysophosphatidic acid (16:0, 18:0, 18:1, 18:2, and 20:4), lysophosphatidylinositol (18:0), lysophosphatidylserine (18:1), lysophosphatidylcholine (16:0,18:0,18:1,18:2, and 20:4), sphingosine-1-phosphate, and sphingosylphosphorylcholine species from human female plasma samples with malignant, benign, or no breast tumor present. Other methods described here include handling patient blood samples, lipid extraction, and factors that affect lysophospholipid production and loss during sample handling.
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页码:1 / +
页数:29
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