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Oxidative stress‐dependent increase in ICAM‐1 expression promotes adhesion of colorectal and pancreatic cancers to the senescent peritoneal mesothelium
Author(s) -
Ksia̧żek Krzysztof,
MikułaPietrasik Justyna,
Catar Rusan,
Dworacki Grzegorz,
Winckiewicz Marek,
Frydrychowicz Magdalena,
Dragun Duska,
Staniszewski Ryszard,
Jörres Achim,
Witowski Janusz
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25036
Subject(s) - mesothelium , oxidative stress , intercellular adhesion molecule 1 , senescence , microbiology and biotechnology , cancer research , cell adhesion molecule , pancreatic cancer , biology , cell culture , cell adhesion , mesothelial cell , cell , pathology , medicine , endocrinology , cancer , biochemistry , genetics
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.