title: Oxidative stress-dependent increase in ICAM-1 expression promotes adhesion of colorectal and pancreatic cancers to the senescent peritoneal mesothelium.
abstract: Intercellular adhesion molecule-1 (ICAM-1) has been implicated in adhesion of colorectal and pancreatic cancer cells (of the SW480 and PSN-1 line, respectively) to the peritoneal mesothelium. It has been demonstrated that ICAM-1 expression increases with senescence in some cell types, however, the significance of this phenomenon in the context of malignant dissemination remains elusive. In this report we show that the adherence of SW480 and PSN-1 cells to senescent human omentum-derived mesothelial cells (HOMCs) in vitro is greater than to early-passage cells and that the effect is mediated by ICAM-1. Senescent HOMCs display increased expression of ICAM-1 mRNA and cell surface protein. The development of this phenotype is related to increased oxidative stress in senescent cells. The augmented ICAM-1 expression in HOMCs can be reduced by culturing cells with antioxidants; in contrast, exposure of HOMCs to an oxidant, t-BHP, leads to cellular senescence and increased ICAM-1 expression. The effect is partly mediated by activation of p38 MAPK and AP-1 signaling pathways. Finally, culture of HOMCs in the presence of a strong antioxidant, PBN, significantly reduces the senescence-associated increase in SW480 and PSN-1 cancer cell binding. These results indicate that increased oxidative stress and increased expression of ICAM-1 in senescent HOMCs may facilitate peritoneal adhesion of selected colorectal and pancreatic cancers.
authors.affiliation: Department of Pathophysiology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ksiazek
authors.forename: Justyna
authors.initials: J
authors.lastname: Mikuła-Pietrasik
authors.forename: Rusan
authors.initials: R
authors.lastname: Catar
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dworacki
authors.forename: Marek
authors.initials: M
authors.lastname: Winckiewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Frydrychowicz
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.forename: Ryszard
authors.initials: R
authors.lastname: Staniszewski
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009852:Omentum / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases