title: Ovarian cancer-derived ascitic fluids induce a senescence-dependent pro-cancerogenic phenotype in normal peritoneal mesothelial cells.
abstract: OBJECTIVE
  After the seeding ovarian cancer cells into the peritoneal cavity, ascitic fluid creates a microenvironment in which these cells can survive and disseminate. The exact nature of the interactions between malignant ascitic fluids and peritoneal mesothelial cells (HPMCs) in ovarian cancer progression has so far remained elusive. Here we assessed whether malignant ascitic fluids may promote the senescence of HPMCs and, by doing so, enhance the acquisition of their pro-cancerogenic phenotype.
  
  
  METHODS
  Primary omentum-derived HPMCs, ovarian cancer-derived cell lines (A2780, OVCAR-3, SKOV-3), malignant ascitic fluids and benign ascitic fluids from non-cancerous patients were used in this study. Ovarian cancer cell proliferation, as well as HPMC proliferation and senescence, were determined using flow cytometry and β-galactosidase assays, respectively. Ovarian cancer cell migration was quantified using a Transwell assay. The concentrations of soluble agents in ascitic fluids, conditioned media and cell lysates were measured using DuoSet® Immunoassay Development kits.
  
  
  RESULTS
  We found that HPMCs, when exposed to malignant ascitic fluids, exhibited decreased proliferation and increased senescence rates. The malignant ascitic fluids were found to contain elevated levels of HGF, TGF-β1 and GRO-1, of which HGF and GRO-1 were able to induce senescence in HPMCs. We also found that HPMCs subjected to malignant ascitic fluids or exogenously added HGF and GRO-1 stimulated ovarian cancer cell progression, which was manifested by an increased production of HA (adhesion), uPA (proliferation), IL-8 and MCP-1 (migration).
  
  
  CONCLUSIONS
  Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Mikuła-Pietrasik
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Uruski
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Matuszkiewicz
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, 60-535, Poznań, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Szubert
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, 60-535, Poznań, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Moszyński
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, 60-535, Poznań, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Szpurek
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, 60-535, Poznań, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sajdak
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tykarski
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland. kksiazek@ump.edu.pl.
authors.forename: Krzysztof
authors.identifier: http://orcid.org/0000-0002-6066-5747
authors.initials: K
authors.lastname: Książek
mesh_terms: D000328:Adult; D001202:Ascitic Fluid; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype
keywords: Cellular senescence; Malignant ascites; Ovarian cancer; Peritoneal mesothelium