title: Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous carcinoma effusions.
abstract: BACKGROUND
  Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy usually presenting with bilateral localization and malignant peritoneal effusion. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived vesicles that participate in intercellular communication, delivering their cargo of molecules to specific cells. Exosomes are involved in several physiological and pathological processes including oncogenesis, immunomodulation, angiogenesis, and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in resected OSC specimens and in cells and exosomes from OSC peritoneal effusions.
  
  
  METHODS
  PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic peritoneal effusions. miR-21 was also evaluated by in situ hybridization.
  
  
  RESULTS
  Immunohistochemistry demonstrated a gradual PDCD4 loss from normal ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens compared with OSC cases and highlighted miR-21 overexpression in OSC specimens. In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21 inverse expression was also noted in cells and exosomes from OSC peritoneal effusions compared with nonneoplastic effusions.
  
  
  CONCLUSIONS
  PDCD4 and miR-21 are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as a diagnostic tool.
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cappellesso
authors.forename: Andrea
authors.initials: A
authors.lastname: Tinazzi
authors.forename: Thomas
authors.initials: T
authors.lastname: Giurici
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonato
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.forename: Laura
authors.initials: L
authors.lastname: Ventura
authors.forename: Marika
authors.initials: M
authors.lastname: Crescenzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Chiarelli
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
mesh_terms: D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins
keywords: exosomes; malignant effusions; microRNA-21 (miR-21); ovarian carcinoma; programmed cell death 4 (PDCD4)