Justyna Mikuła-Pietrasik1, Paweł Uruski1, Kinga Matuszkiewicz1, Sebastian Szubert2, Rafał Moszyński2, Dariusz Szpurek2, Stefan Sajdak2, Andrzej Tykarski1, Krzysztof Książek3. 1. Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland. 2. Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, 60-535, Poznań, Poland. 3. Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848, Poznań, Poland. kksiazek@ump.edu.pl.
Abstract
PURPOSE: 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). CONCLUSION: Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.
PURPOSE: 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-cancerouspatients 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). CONCLUSION: Our results indicate that malignant ascitic fluids may contribute to ovarian cancer progression by accelerating the senescence of HPMCs.
Authors: K Fischer; V Lutz; O Wilhelm; M Schmitt; H Graeff; P Heiss; T Nishiguchi; N Harbeck; H Kessler; T Luther; V Magdolen; U Reuning Journal: FEBS Lett Date: 1998-10-30 Impact factor: 4.124
Authors: Hilary A Kenny; Chun-Yi Chiang; Erin A White; Elizabeth M Schryver; Mohammed Habis; Iris L Romero; Andras Ladanyi; Carla V Penicka; Joshy George; Karl Matlin; Anthony Montag; Kristen Wroblewski; S Diane Yamada; Andrew P Mazar; David Bowtell; Ernst Lengyel Journal: J Clin Invest Date: 2014-09-09 Impact factor: 14.808
Authors: Krzysztof Ksiazek; Justyna Mikula-Pietrasik; Katarzyna Korybalska; Grzegorz Dworacki; Achim Jörres; Janusz Witowski Journal: Am J Pathol Date: 2009-02-26 Impact factor: 4.307
Authors: Jacob P Veenstra; Lucas Felipe Fernandes Bittencourt; Katherine M Aird Journal: Am J Physiol Cell Physiol Date: 2022-05-18 Impact factor: 5.282