title: Senescent peritoneal mesothelium creates a niche for ovarian cancer metastases.
abstract: Although both incidence and aggressiveness of ovarian malignancy rise with age, the exact reason for this tendency, in particular the contribution of senescent cells, remains elusive. In this project we found that the patient's age determines the frequency of intraperitoneal metastases of ovarian cancer. Moreover, we documented that senescent human peritoneal mesothelial cells (HPMCs) stimulate proliferation, migration and invasion of ovarian cancer cells in vitro, and that this effect is related to both the activity of soluble agents released to the environment by these cells and direct cell-cell contact. The panel of mediators of the pro-cancerous activity of senescent HPMCs appeared to be cancer cell line-specific. The growth of tumors in a mouse peritoneal cavity was intensified when the cancer cells were co-injected together with senescent HPMCs. This effect was reversible when the senescence of HPMCs was slowed down by the neutralization of p38 MAPK. The analysis of lesions excised from the peritoneum of patients with ovarian cancer showed the abundance of senescent HPMCs in close proximity to the cancerous tissue. Collectively, our findings indicate that senescent HPMCs which accumulate in the peritoneum in vivo may create a metastatic niche facilitating intraperitoneal expansion of ovarian malignancy.
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., Poznań 61-848, 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., Poznań 61-848, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Uruski
authors.affiliation: Department of Pathophysiology; Poznań University of Medical Sciences, Rokietnicka 8 Str., Poznań 60-806, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sosińska
authors.affiliation: Department of Clinical Pathology, Poznań University of Medical Sciences, Przybyszewskiego 49 Str., Poznań 60-355, Poland.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Maksin
authors.affiliation: Department of Toxicology; Poznań University of Medical Sciences, Dojazd 30 Str., Poznań 60-631, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Piotrowska-Kempisty
authors.affiliation: Department of Toxicology; Poznań University of Medical Sciences, Dojazd 30 Str., Poznań 60-631, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kucińska
authors.affiliation: Department of Toxicology; Poznań University of Medical Sciences, Dojazd 30 Str., Poznań 60-631, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, Poznań 60-535, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Szubert
authors.affiliation: Department of Clinical Pathology, Poznań University of Medical Sciences, Przybyszewskiego 49 Str., Poznań 60-355, Poland.
authors.forename: Aldona
authors.initials: A
authors.lastname: Woźniak
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, Poznań 60-535, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Szpurek
authors.affiliation: Division of Gynecological Surgery, Poznań University of Medical Sciences, Polna 33 Str, Poznań 60-535, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sajdak
authors.affiliation: Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, Warsaw 02-093, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piwocka
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., Poznań 61-848, 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., Poznań 61-848, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Książek
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000473:pathology*; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018450:Disease Progression; D004848:Epithelium / Q000187:drug effects / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010537:Peritoneum / Q000473:pathology*; D010641:Phenotype; D012995:Solubility; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D048051:p38 Mitogen-Activated Protein Kinases