title: Phosphatidylcholine-specific phospholipase C activation in epithelial ovarian cancer cells.
abstract: Elucidation of the mechanisms responsible for aberrant phosphatidylcholine (PC) metabolism in cancer cells may allow identification of novel biomarkers of tumor progression and design of new targeted anticancer therapies. We recently reported up-regulation of PC-specific phospholipases in epithelial ovarian cancer cells (EOC) compared with nontumoral (normal or immortalized) counterparts (EONT). In the present study, we focused, in the same cell systems, on levels, subcellular localization, and activity of PC-specific phospholipase C (PC-PLC), for which a key role in cell proliferation, differentiation, and apoptosis has been shown in several mammalian cells. A 66-kDa PC-PLC isoform, detected in nuclear and cytoplasmic compartments of both EOC and EONT cells, accumulated on the external plasma membrane of cancer cells only, where it colocalized with beta1 integrin, in nonraft membrane domains. PC-PLC activity was 3-fold higher in total cell lysates and 5-fold higher in membrane-enriched fractions of EOC compared with EONT cells. Serum deprivation induced in EOC, but not in EONT, cells a 3-fold decrease in PC-PLC activity, associated with a 40% drop in S-phase fraction. The recovery of both variables to their original levels in serum-restimulated (or lysophosphatidic acid-restimulated) EOC cells was strongly delayed, for at least 24 h, in the presence of the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609). The S-phase of serum-restimulated EONT cells was not sensitive to D609. These findings warrant further investigations on the role of PC-PLC and on the effects of its inhibition on the pathways responsible for constitutive EOC cell stimulation and cell proliferation.
authors.affiliation: Section of Molecular and Cellular Imaging, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramoni
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.forename: Silvia
authors.initials: S
authors.lastname: Miotti
authors.forename: Paola
authors.initials: P
authors.lastname: Alberti
authors.forename: Serena
authors.initials: S
authors.lastname: Cecchetti
authors.forename: Egidio
authors.initials: E
authors.lastname: Iorio
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolo
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Franca
authors.initials: F
authors.lastname: Podo
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000556:secondary; D017209:Apoptosis / Q000502:physiology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000556:secondary; D002462:Cell Membrane / Q000201:enzymology / Q000473:pathology; D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000556:secondary; D003593:Cytoplasm / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D021962:Membrane Microdomains; D009636:Norbornanes; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D010053:Ovary / Q000201:enzymology / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D019098:Telomerase / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001952:Bridged-Ring Compounds; D016895:Culture Media, Serum-Free; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; C509186:TERT protein, human; D019098:Telomerase; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D010739:Phospholipase D