lysophosphatidylethanolamine and Ovarian-Neoplasms

High performance mass spectrometry was employed to interrogate the serum metabolome of early-stage ovarian cancer (OC) patients and age-matched control women. The resulting spectral features were used to establish a linear support vector machine (SVM) model of sixteen diagnostic metabolites that are able to identify early-stage OC with 100% accuracy in our patient cohort. The results provide evidence for the importance of lipid and fatty acid metabolism in OC and serve as the foundation of a clinically significant diagnostic test.

Topics: Adult; Aged; Biomarkers, Tumor; CA-125 Antigen; Case-Control Studies; Chromatography, High Pressure Liquid; Early Detection of Cancer; Female; Humans; Lysophospholipids; Metabolome; Metabolomics; Middle Aged; Ovarian Neoplasms; Principal Component Analysis; Sensitivity and Specificity; Support Vector Machine; Tandem Mass Spectrometry

We investigated whether lysophosphatidylethanolamine (LPE) modulates cellular signaling in different cell types. SK-OV3 ovarian cancer cells and OVCAR-3 ovarian cancer cells were responsive to LPE. LPE-stimulated intracellular calcium concentration ([Ca(2+)](i)) increase was inhibited by U-73122, suggesting that LPE stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca(2+)](i) increase by LPE, indicating the involvement of PTX-sensitive G-proteins. Furthermore, we found that LPE stimulated chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. We examined the role of lysophosphatidic acid receptors on LPE-stimulated cellular responses using HepG2 cells transfected with different LPA receptors, and found that LPE failed to stimulate nuclear factor kappa B-driven luciferase. We suggest that LPE stimulates a membrane bound receptor, different from well known LPA receptors, resulting in chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells.

Topics: Calcium; Cell Line, Tumor; Cell Movement; Chemotaxis; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; GTP-Binding Proteins; HeLa Cells; Humans; Luciferases; Lysophospholipids; Neoplasm Invasiveness; Ovarian Neoplasms; Pertussis Toxin; Receptors, G-Protein-Coupled; Receptors, Lysophosphatidic Acid; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transfection; Type C Phospholipases; U937 Cells