The Influence of Reactive Oxygen Species on the Adhesion of Pancreatic Carcinoma Cells to the Peritoneum

Raa, Sander Ten; Grevenstein, Helma M.U. van; Kate, Miranda ten; Mangundap, Kristin M.; Hofland, Leo J.; Jeekel, Hans; Sluiter, Wim J.; Eijck, Casper H.J. van

doi:10.4161/cam.1.2.4283

Cited by 9 publications

(13 citation statements)

References 24 publications

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“…Physical stress, for example by surgery, or chemical injury to the peritoneum, provokes a sterile local inflammation, which is a privileged site of tumor recurrence (10,16,38,39). The up-regulation of adhesion molecules on HMCs is regarded as causal mechanism behind this observance (30,40).…”

Section: Discussionmentioning

confidence: 99%

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Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and β1 integrin

et al. 2011

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Abstract. Peritoneal carcinomatosis describes cancer metastasis onto the surface of the peritoneum. It is frequently caused by ovarian and colorectal cancer. Once a tumor has penetrated the peritoneum, cancer cells disseminate into the abdominal cavity. Additionally, surgery can account for the spread of free tumor cells. Their subsequent adhesion to mesothelial cells (HMCs) initiates peritoneal carcinomatosis. Therefore, this study analyzed the effect of simvastatin on tumor cell adherence. HMCs were isolated from human greater omentum. Fluorescence-labeled tumor cells (SKOV-3, OvCar-29, OAW42, FraWü; ovarian/HT29; colorectal) were incubated on confluent mesothelial monolayers with 10 µM simvastatin for 48 h. Adhesion was quantified using a fluorescence reader. Expression of the adhesion molecules VCAM-1, ICAM-1 and β 1 integrin chain under the influence of simvastatin 0.1-100 µM for 24-72 h was analyzed using flow cytometry. Simvastatin significantly reduced the adhesion of all ovarian cancer cells and HT29 to HMCs (P≤0.001). Concomitantly simvastatin decreased the expression of VCAM-1 on HMCs. ICAM-1 and β 1 integrin chain expression on ovarian cancer cells was also clearly reduced. By contrast, the expression of the analyzed adhesion molecules on HT29 cells remained unchanged. Simvastatin clearly inhibits tumor cell adhesion to HMCs. In the case of ovarian cancer cell lines it appears to be mediated by decreased expression of both VCAM-1 on HMCs and the integrin α 4 β 1 on tumor cells. As an example of adhesion molecule down-regulating drugs, simvastatin may provide a novel therapeutic approach to the prevention of peritoneal carcinomatosis.

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Section: Discussionmentioning

confidence: 99%

“…(ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 on HMCs (15,16). Ovarian cancer cell adhesion to HMCs is dependent on VCAM-1 (17).…”

Section: Simvastatin Reduces Tumor Cell Adhesion To Human Peritoneal mentioning

confidence: 99%

Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and β1 integrin

et al. 2011

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“…Incubation of colon cancer cells with XO is associated with an increase in the adhesive capabilities of colon cancer cells to a mesothelial and endothelial monolayer in an integrin α 2 β 1 dependent manner 3. XO incubation is also associated with increased expression of adhesion molecules ICAM-1, VCAM-1 and CD44h 3 136 137…”

Section: Oncological Implications Of Surgery-induced Redox Signallingmentioning

confidence: 99%

Less stress, more success? Oncological implications of surgery-induced oxidative stress

O’Leary

Wang

Cotter

et al. 2011

Gut

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Reactive oxygen species (ROS) possess important cell signalling properties. This contradicts traditional thought which associated ROS activity with cell death. Emerging evidence clearly demonstrates that ROS signalling acts as a key regulator in tumour cell survival and in the cellular processes required for tumour cells to successfully metastasise and proliferate. The discovery of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) family of enzymes in the last decade has unravelled much of the mystery surrounding how ROS are generated. Tumour cells are now known to express Nox enzymes which produce ROS required for cellular signalling. Activation of Nox enzymes occurs via interaction with proinflammatory cytokines and growth factors, all of which are released following surgical trauma. As our understanding of the signalling capabilities of ROS grows, the oncological implications of ROS activity are gradually being revealed. Nox-derived ROS are known to play a central role in each step of the metastatic cascade including invasion, adhesion, angiogenesis and proliferation. This article describes how surgery creates a ROS-rich environment, which facilitates redox signalling, and also examines the role played by Nox enzymes in this process. The authors then explore current knowledge of the oncological implications of surgery-induced redox signalling, and discuss current and future therapeutic strategies targeted at ROS and Nox enzymes in cancer patients.

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“…This, however, does not completely prevent tumour cell adherence and proliferation [18]. Changes in the peritoneal mesothelial microenvironment and resulting milieu after laparoscopy are capable of increasing the invasive potential of shed cancer cells via EMT and MMT [9,70,71,74,75,78,81]. Epithelial-mesenchymal transition (EMT) related to hypoxia, HIF-1α release, acidosis and CO 2 insufflation may still occur despite WH CO 2 conditioning or use of lower pneumoperitoneum IAP [18,48,50,78].…”

Section: Prevention Of Tumour Implantation By Warm Humidified Comentioning

confidence: 99%

“…Peritoneal acidosis and CO 2 insufflation results in local production of IL-1β, IL-6 and TNFα [11,14]. Tissue adhesion molecules (ICAM, VCAM, CD44H) in human peritoneal mesothelial cells are upregulated by ROS, TNFα, IL-1β and IL-8, which can enhance the initial attachment of pancreatic carcinoma cells to the peritoneum [74,75]. Peritoneal acidosis (pH = 6.1) during CO 2 -pneumoperitoneum increases colon carcinoma cell, but not mesothelial cell, expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1).…”

Section: Peritoneal Climate Change Favours Tumour Cell Implantation Amentioning

confidence: 99%

Changes in the coelomic microclimate during carbon dioxide laparoscopy: morphological and functional implications

Wilson

2017

Pleura and Peritoneum

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In this article the adverse effects of laparoscopic CO 2 -pneumoperitoneum and coelomic climate change, and their potential prevention by warmed, humidified carbon dioxide insufflation are reviewed. The use of pressurized cold, dry carbon dioxide (C0 2 ) pneumoperitoneum causes a number of local effects on the peritoneal mesothelium, as well as systemic effects. These can be observed at a macroscopic, microscopic, cellular and metabolic level. Local effects include evaporative cooling, oxidative stress, desiccation of mesothelium, disruption of mesothelial cell junctions and glycocalyx, diminished scavenging of reactive oxygen species, decreased peritoneal blood flow, peritoneal acidosis, peritoneal hypoxia or necrosis, exposure of the basal lamina and extracellular matrix, lymphocyte infiltration, and generation of peritoneal cytokines such as IL-1, IL-6, IL-8 and TNFα. Such damage is increased by high CO 2 insufflation pressures and gas velocities and prolonged laparoscopic procedures. The resulting disruption of the glycocalyx, mesothelial cell barrier and exposure of the extracellular matrix creates a cascade of immunological and proinflammatory events and favours tumour cell implantation. Systemic effects include cardiopulmonary and respiratory changes, hypothermia and acidosis. Such coelomic climate change can be prevented by the use of lower insufflation pressures and preconditioned warm humidified CO 2 . By achieving a more physiological temperature, pressure and humidity, the coelomic microenvironment can be better preserved during pneumoperitoneum. This has the potential clinical benefits of maintaining isothermia and perfusion, reducing postoperative pain, preventing adhesions and inhibiting cancer cell implantation in laparoscopic surgery.

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The Influence of Reactive Oxygen Species on the Adhesion of Pancreatic Carcinoma Cells to the Peritoneum

Cited by 9 publications

References 24 publications

Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and β1 integrin

Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and β1 integrin

Less stress, more success? Oncological implications of surgery-induced oxidative stress

Changes in the coelomic microclimate during carbon dioxide laparoscopy: morphological and functional implications

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