Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids.

Lysophospholipids (lyso-PLs), including various glycerol-based and sphingosine-based lysophospholipids, play important roles in many biochemical, physiological, and pathological processes. The classical methods to analyze these lipids involve gas chromatography and/or high-performance liquid chromatography, which are time-consuming, cumbersome, and sometimes inaccurate due to the incomplete separation of closely related lipid species. We now describe the quantitative analysis of lyso-PLs in ascites samples from patients with ovarian cancer using electrospray ionization spectrometry. Three new classes of lyso-PL molecules are detected: alkyl-LPA, alkenyl-LPA, and methylated lysophosphatidylethanolamine. Importantly, the following lysophospholipid species are significantly increased in ascites from patients with ovarian cancer, compared to patients with nonmalignant diseases (e.g., liver failure): LPA (including acyl-, alkyl-, and alkenyl-LPA species), lysophosphatidylinositol, and sphingosylphosphorylcholine. Lysophosphorylcholine contents are also significantly different among ascitic fluids from the two groups of patients. However, the total phosphate content in ascites samples from patients with ovarian cancer is not significantly different compared to that from patients with nonmalignant disease.

[1]  K. Liliom,et al.  Naturally occurring analogs of lysophosphatidic acid elicit different cellular responses through selective activation of multiple receptor subtypes. , 1998, Molecular pharmacology.

[2]  F. Hirata,et al.  Phospholipid methylation and biological signal transmission. , 1980, Science.

[3]  L. Cantley,et al.  Lipid second messengers , 2017 .

[4]  M Markman,et al.  Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. , 1998, JAMA.

[5]  Y Chen,et al.  Evaluation of Plasma Lysophospholipids for Diagnostic Significance Using Electrospray Ionization Mass Spectrometry (ESI‐MS) Analyses , 2000, Annals of the New York Academy of Sciences.

[6]  K. Liliom,et al.  Xenopus oocytes express multiple receptors for LPA-like lipid mediators. , 1996, The American journal of physiology.

[7]  W. Moolenaar.  Development of Our Current Understanding of Bioactive Lysophospholipids , 2000, Annals of the New York Academy of Sciences.

[8]  M. Bookman.  Biological therapy of ovarian cancer: current directions. , 1998, Seminars in oncology.

[9]  L. Douste-Blazy,et al.  Human platelet aggregation induced by 1-alkyl-lysophosphatidic acid and its analogs: a new group of phospholipid mediators? , 1982, Biochemical and biophysical research communications.

[10]  K. Fukuzawa,et al.  Positive and negative controls by protein kinases of sodium-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells stimulated by lysophosphatidic acid. , 1998, Biochimica et biophysica acta.

[11]  G. Mills,et al.  Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. , 1990, The Journal of clinical investigation.

[12]  S. S. Chen,et al.  High-performance liquid chromatography of methylated phospholipids. , 1982, Journal of chromatography.

[13]  Yan Xu,et al.  Sphingosine‐1‐phosphate modulates growth and adhesion of ovarian cancer cells , 1999, FEBS letters.

[14]  G. Mills,et al.  Lysophospholipids activate ovarian and breast cancer cells. , 1995, The Biochemical journal.

[15]  D. Hanahan,et al.  Signaling responses to alkyllysophosphatidic acid: the activation of phospholipases A2 and C and protein tyrosine phosphorylation in human platelets. , 1996, Archives of biochemistry and biophysics.

[16]  H. Homma,et al.  Structural analogs of alkylacetylglycerophosphocholine inhibitory behavior on platelet activation. , 1985, The Journal of biological chemistry.

[17]  K. Jakobs,et al.  Molecular diversity of sphingolipid signalling , 1997, FEBS letters.

[18]  K. Fukuzawa,et al.  Effects of lysophosphatidic acids and their structural analogs on arterial blood pressure of cats. , 1985, Arzneimittel-Forschung.

[19]  S. Spiegel.  Sphingosine 1‐phosphate: a prototype of a new class of second messengers , 1999, Journal of leukocyte biology.

[20]  O. Kranenburg,et al.  Lysophosphatidic acid: G-protein signalling and cellular responses. , 1997, Current opinion in cell biology.

[21]  G. Mills,et al.  A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. , 1988, Cancer research.

[22]  S. Rodenhuis,et al.  Growth factors in human ovarian cancer. , 1997, Cancer treatment reviews.

[23]  K. Waku,et al.  Occurrence of lysophosphatidic acid and its alkyl ether-linked analog in rat brain and comparison of their biological activities toward cultured neural cells. , 1999, Biochimica et biophysica acta.

[24]  G. Mills,et al.  Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  A. Samad,et al.  Metabolism of phospholipids and lysophospholipids by Trypanosoma brucei. , 1988, Molecular and biochemical parasitology.

[26]  A. Berchuck,et al.  Human ovarian cancer of the surface epithelium. , 1997, Biochemical pharmacology.

[27]  Duane D. Miller,et al.  Identification of a Novel Growth Factor-like Lipid, 1-O-cis-Alk-1′-enyl-2-lyso-sn-glycero-3-phosphate (Alkenyl-GP) That Is Present in Commercial Sphingolipid Preparations* , 1998, The Journal of Biological Chemistry.