Lipidomic approach to identify patterns in phospholipid profiles and define class differences in mammary epithelial and breast cancer cells
Tóm tắt
Breast cancer is the leading cause of cancer-related deaths in women. Altered cellular functions of cancer cells lead to uncontrolled cellular growth and morphological changes. Cellular biomembranes are intimately involved in the regulation of cell signaling; however, they remain largely understudied. Phospholipids (PLs) are the main constituents of biological membranes and play important functional, structural and metabolic roles. The aim of this study was to establish if patterns in the PL profiles of mammary epithelial cells and breast cancer cells differ in relation to degree of differentiation and metastatic potential. For this purpose, PLs were analyzed using a lipidomic approach. In brief, PLs were extracted using Bligh and Dyer method, followed by a separation of PL classes by thin layer chromatography, and subsequent analysis by mass spectrometry (MS). Differences and similarities were found in the relative levels of PL content between mammary epithelial and breast cancer cells and between breast cancer cells with different levels of aggressiveness. When compared to the total PL content, phosphatidylcholine levels were reduced and lysophosphatydilcholines increased in the more aggressive cancer cells; while phosphatidylserine levels remained unchanged. MS analysis showed alterations in the classes of phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and phosphatidylinositides. In particular, the phosphatidylinositides, which are signaling molecules that affect proliferation, survival, and migration, showed dramatic alterations in their profile, where an increase of phosphatdylinositides saturated fatty acids chains and a decrease in C20 fatty acids in cancer cells compared with mammary epithelial cells was observed. At present, information about PL changes in cancer progression is lacking. Therefore, these data will be useful as a starting point to define possible PLs with prospective as biomarkers and disclose metabolic pathways with potential for therapy.
Tài liệu tham khảo
Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150. doi:10.1200/JCO.2005.05.2308
Fernandis AZ, Wenk MR (2009) Lipid-based biomarkers for cancer. J Chromatogr B Analyt Technol Biomed Life Sci 877(26):2830–2835. doi:10.1016/j.jchromb.2009.06.015
Escriba PV, Gonzalez-Ros JM, Goni FM, Kinnunen PK, Vigh L, Sanchez-Magraner L, Fernandez AM, Busquets X, Horvath I, Barcelo-Coblijn G (2008) Membranes: a meeting point for lipids, proteins and therapies. J Cell Mol Med 12(3):829–875. doi:10.1111/j.1582-4934.2008.00281.x
Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH Jr, Murphy RC, Raetz CR, Russell DW, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, VanNieuwenhze MS, White SH, Witztum JL, Dennis EA (2005) A comprehensive classification system for lipids. J Lipid Res 46(5):839–861. doi:10.1194/jlr.E400004-JLR200
van Meer G, de Kroon AI (2011) Lipid map of the mammalian cell. J Cell Sci 124(Pt 1):5–8. doi:10.1242/jcs.071233
Wymann MP, Schneiter R (2008) Lipid signalling in disease. Nat Rev Mol Cell Biol 9(2):162–176. doi:10.1038/nrm2335
Patra SK (2008) Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta Rev Cancer 1785(2):182–206. doi:10.1016/j.bbcan.2007.11.002
Ackerstaff E, Glunde K, Bhujwalla ZM (2003) Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90(3):525–533. doi:10.1002/jcb.10659
Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443(7112):651–657. doi:10.1038/nature05185
Bian D, Su S, Mahanivong C, Cheng RK, Han Q, Pan ZK, Sun P, Huang S (2004) Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res 64(12):4209–4217. doi:10.1158/0008-5472.CAN-04-0060
Causeret M, Taulet N, Comunale F, Favard C, Gauthier-Rouviere C (2005) N-cadherin association with lipid rafts regulates its dynamic assembly at cell–cell junctions in C2C12 myoblasts. Mol Biol Cell 16(5):2168–2180. doi:10.1091/mbc.E04-09-0829
Patra SK (2008) Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta 1785(2):182–206. doi:10.1016/j.bbcan.2007.11.002
Paschos KA, Canovas D, Bird NC (2009) The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis. Cell Signal 21(5):665–674. doi:10.1016/j.cellsig.2009.01.006
Merchant TE, Kasimos JN, Vroom T, de Bree E, Iwata JL, de Graaf PW, Glonek T (2002) Malignant breast tumor phospholipid profiles using P-31 magnetic resonance. Cancer Lett 176(2):159–167
Merchant TE, Meneses P, Gierke LW, Den Otter W, Glonek T (1991) 31P magnetic resonance phospholipid profiles of neoplastic human breast tissues. Br J Cancer 63(5):693–698
Zehethofer N, Pinto DM (2008) Recent developments in tandem mass spectrometry for lipidomic analysis. Anal Chim Acta 627(1):62–70. doi:10.1016/j.aca.2008.06.045
Watson AD (2006) Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res 47(10):2101–2111. doi:10.1194/jlr.R600022-JLR200
Pulfer M, Murphy RC (2003) Electrospray mass spectrometry of phospholipids. Mass Spectrom Rev 22(5):332–364. doi:10.1002/mas.10061
Dill AL, Ifa DR, Manicke NE, Costa AB, Ramos-Vara JA, Knapp DW, Cooks RG (2009) Lipid profiles of canine invasive transitional cell carcinoma of the urinary bladder and adjacent normal tissue by desorption electrospray ionization imaging mass spectrometry. Anal Chem 81(21):8758–8764. doi:10.1021/ac901028b
Kim Y, Shanta SR, Zhou LH, Kim KP (2010) Mass spectrometry based cellular phosphoinositides profiling and phospholipid analysis: a brief review. Exp Mol Med 42(1):1–11. doi:10.3858/emm.2010.42.1.001
Kim H, Min HK, Kong G, Moon MH (2009) Quantitative analysis of phosphatidylcholines and phosphatidylethanolamines in urine of patients with breast cancer by nanoflow liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem 393(6–7):1649–1656. doi:10.1007/s00216-009-2621-3
Min HK, Kong G, Moon MH (2010) Quantitative analysis of urinary phospholipids found in patients with breast cancer by nanoflow liquid chromatography-tandem mass spectrometry: II. Negative ion mode analysis of four phospholipid classes. Anal Bioanal Chem 396(3):1273–1280. doi:10.1007/s00216-009-3292-9
Reichmann E, Schwarz H, Deiner EM, Leitner I, Eilers M, Berger J, Busslinger M, Beug H (1992) Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion. Cell 71(7):1103–1116
Lanari C, Luthy I, Lamb CA, Fabris V, Pagano E, Helguero LA, Sanjuan N, Merani S, Molinolo AA (2001) Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins. Cancer Res 61(1):293–302
Blixt Y, Valeur A, Everitt E (1990) Cultivation of HeLa cells with fetal bovine serum or Ultroser G: effects on the plasma membrane constitution. In Vitro Cell Dev Biol 26(7):691–700
Elliott WM, Auersperg N (1993) Growth of normal human ovarian surface epithelial cells in reduced-serum and serum-free media. In Vitro Cell Dev Biol 29A(1):9–18
Spence MW, Byers DM, Palmer FB, Cook HW (1989) A new Zn2+-stimulated sphingomyelinase in fetal bovine serum. J Biol Chem 264(10):5358–5363
Warden CH, Friedkin M (1984) Regulation of phosphatidylcholine biosynthesis by mitogenic growth factors. Biochim Biophys Acta 792(3):270–280
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917
Zhou X, Arthur G (1992) Improved procedures for the determination of lipid phosphorus by malachite green. J Lipid Res 33(8):1233–1236
Fuchs B, Suss R, Teuber K, Eibisch M, Schiller J (2011) Lipid analysis by thin-layer chromatography—a review of the current state. J Chromatogr A 1218(19):2754–2774. doi:10.1016/j.chroma.2010.11.066
Koivusalo M, Haimi P, Heikinheimo L, Kostiainen R, Somerharju P (2001) Quantitative determination of phospholipid compositions by ESI-MS: effects of acyl chain length, unsaturation, and lipid concentration on instrument response. J Lipid Res 42(4):663–672
Sterin M, Cohen JS, Ringel I (2004) Hormone sensitivity is reflected in the phospholipid profiles of breast cancer cell lines. Breast Cancer Res Treat 87(1):1–11
Han X, Gross RW (2005) Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev 24(3):367–412. doi:10.1002/mas.20023
Hsu FF, Turk J (2009) Electrospray ionization with low-energy collisionally activated dissociation tandem mass spectrometry of glycerophospholipids: mechanisms of fragmentation and structural characterization. J Chromatogr B Analyt Technol Biomed Life Sci 877(26):2673–2695. doi:10.1016/j.jchromb.2009.02.033
Katz-Brull R, Seger D, Rivenson-Segal D, Rushkin E, Degani H (2002) Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. Cancer Res 62(7):1966–1970
Olayioye MA, Vehring S, Muller P, Herrmann A, Schiller J, Thiele C, Lindeman GJ, Visvader JE, Pomorski T (2005) StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein. J Biol Chem 280(29):27436–27442. doi:10.1074/jbc.M413330200
Hoffmann P, Olayioye MA, Moritz RL, Lindeman GJ, Visvader JE, Simpson RJ, Kemp BE (2005) Breast cancer protein StarD10 identified by three-dimensional separation using free-flow electrophoresis, reversed-phase high-performance liquid chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoresis 26(6):1029–1037. doi:10.1002/elps.200406197
Murphy NC, Biankin AV, Millar EK, McNeil CM, O’Toole SA, Segara D, Crea P, Olayioye MA, Lee CS, Fox SB, Morey AL, Christie M, Musgrove EA, Daly RJ, Lindeman GJ, Henshall SM, Visvader JE, Sutherland RL (2010) Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status. Int J Cancer 126(6):1445–1453. doi:10.1002/ijc.24826
Murakami M, Kudo I (2002) Phospholipase A2. J Biochem 131(3):285–292
Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K, Ogawa M (1993) Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells. Cancer 71(10):3058–3064
Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 158(2):227–233. doi:10.1083/jcb.200204026
Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K (2002) Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 277(42):39436–39442. doi:10.1074/jbc.M205623200
Yang SY, Lee J, Park CG, Kim S, Hong S, Chung HC, Min SK, Han JW, Lee HW, Lee HY (2002) Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clin Exp Metastasis 19(7):603–608
Xu Y, Shen Z, Wiper DW, Wu M, Morton RE, Elson P, Kennedy AW, Belinson J, Markman M, Casey G (1998) Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 280(8):719–723
Ogretmen B (2006) Sphingolipids in cancer: regulation of pathogenesis and therapy. FEBS Lett 580(23):5467–5476. doi:10.1016/j.febslet.2006.08.052
Hsu FF, Turk J (2000) Structural determination of sphingomyelin by tandem mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom 11(5):437–449
Koyanagi S, Kuga M, Soeda S, Hosoda Y, Yokomatsu T, Takechi H, Akiyama T, Shibuya S, Shimeno H (2003) Elevation of de novo ceramide synthesis in tumor masses and the role of microsomal dihydroceramide synthase. Int J Cancer 105(1):1–6. doi:10.1002/ijc.11024
Kim CW, Lee HM, Lee TH, Kang C, Kleinman HK, Gho YS (2002) Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res 62(21):6312–6317
Seijo L, Merchant TE, van der Ven LT, Minsky BD, Glonek T (1994) Meningioma phospholipid profiles measured by 31P nuclear magnetic resonance spectroscopy. Lipids 29(5):359–364
Vance JE, Steenbergen R (2005) Metabolism and functions of phosphatidylserine. Prog Lipid Res 44(4):207–234. doi:10.1016/j.plipres.2005.05.001
Shi J, Pipe SW, Rasmussen JT, Heegaard CW, Gilbert GE (2008) Lactadherin blocks thrombosis and hemostasis in vivo: correlation with platelet phosphatidylserine exposure. J Thromb Haemost 6(7):1167–1174. doi:10.1111/j.1538-7836.2008.03010.x
Wolfs JL, Comfurius P, Rasmussen JT, Keuren JF, Lindhout T, Zwaal RF, Bevers EM (2005) Activated scramblase and inhibited aminophospholipid translocase cause phosphatidylserine exposure in a distinct platelet fraction. Cell Mol Life Sci 62(13):1514–1525. doi:10.1007/s00018-005-5099-y
Stace CL, Ktistakis NT (2006) Phosphatidic acid- and phosphatidylserine-binding proteins. Biochim Biophys Acta 1761(8):913–926. doi:10.1016/j.bbalip.2006.03.006
Yeung T, Gilbert GE, Shi J, Silvius J, Kapus A, Grinstein S (2008) Membrane phosphatidylserine regulates surface charge and protein localization. Science 319(5860):210–213. doi:10.1126/science.1152066
Dobrzynska I, Szachowicz-Petelska B, Sulkowski S, Figaszewski Z (2005) Changes in electric charge and phospholipids composition in human colorectal cancer cells. Mol Cell Biochem 276(1–2):113–119. doi:10.1007/s11010-005-3557-3
Jiang BH, Liu LZ (2008) PI3K/PTEN signaling in tumorigenesis and angiogenesis. Biochim Biophys Acta 1784(1):150–158. doi:10.1016/j.bbapap.2007.09.008
Larijani B, Dufourc EJ (2006) Polyunsaturated phosphatidylinositol and diacylglycerol substantially modify the fluidity and polymorphism of biomembranes: a solid-state deuterium NMR study. Lipids 41(10):925–932