Marker Of Mesothelial Cells Research Articles

Human Omental Microvascular Endothelial and Mesothelial Cells: Characterization of Two Distinct Mesodermally Derived Epithelial Cells

Human omental microvascular endothelial (HOME) and mesothelial (MESO) cells share many phenotypic properties, but can be characterized from one another based upon a comprehensive panel of endothelial and mesothelial markers. Traditional cell markers such as vonWillebrand factor, DiI-Ac-LDL, andUlex europaeusI lectin are not sufficient to distinguish between HOME and MESO cells. Furthermore, immunoreactivity to a panel of endothelial cell-specific monoclonal antibodies, including representatives from the known clusters of differentiation (CD), indicate that some of these antigens are coexpressed in HOME and MESO cells. In distinguishing between the two cell types, HOME and not MESO cells express E-selectin, E/P-selectin, P-selectin (CD62), Le-y, and VLA-6 (CDw49f*). Moreover, HOME cells and not MESO cells form tube-like structures when cultured on Matrigel. MESO cells differ from HOME cells based upon (1) the expression of cytokeratins; (2) their rapid proliferation in response to platelet-derived growth factor; and (3) a change from an epitheliod to fibroblast-like morphology in response to tumor necrosis factor and epidermal growth factor. Both HOME and MESO cells express tissue plasminogen activator and plasminogen activator inhibitor, but urokinase activity is only expressed by MESO cells. As there is no one universal endothelial or mesothelial cell marker that can specifically confirm the identity of these cells, it appears necessary to employ a comprehensive panel of cell markers to rule out the possibility of misidentifying a cell culture.

Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression.

Histological diagnosis of malignant mesothelioma and differentiation from adenocarcinoma is often difficult. Definitive pathological confirmation of malignant mesothelioma requires demonstration of an appropriate immunohistochemical phenotype. Selection of an optimum panel of immunohistochemical antibodies for the reliable identification of malignant mesothelioma is hindered by the absence of a specific immunohistochemical label for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has been developed as a sensitive mesothelial cell marker. We have compared the immunohistochemical staining patterns achieved with CA125 and HBME-1 to those obtained using a panel of eight further antibodies in 17 malignant mesotheliomas and 14 primary and secondary adenocarcinomas within lung and pleura. CA125 labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17 cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%). BerEP4 positively labelled one malignant mesothelioma but was negative in the remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%). Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient specificity to be useful for differentiating malignant mesothelioma from adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of malignant mesothelioma unlikely. As there remains an absence of a specific positive mesothelial cell marker this distinction is still most reliably made using a panel of antibodies including at least two of the following: anti-CEA, AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of neutral mucin production.

Impaired Initial Cell Reaction in Capd-Related Peritonitis

Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.

The differential expression of N-cadherin and E-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas

Malignant mesotheliomas are highly aggressive tumors that develop most frequently in the pleura of patients chronically exposed to asbestos. The distinction between malignant mesotheliomas and tumors of epithelial origin, particularly peripheral lung adenocarcinoma, can be difficult despite the use of immunocytochemical markers and other diagnostic tools. During embryonic development the cadherin cell-cell adhesion molecules participate in the segregation of cells into different tissues. As a result of complex mechanisms of tissue selectivity, N-cadherin is expressed by the developing pleural mesothelial cells and E-cadherin is expressed by the epithelial cells of the lung. Thus, we postulated that N-cadherin could be used as a marker of mesothelial cells and mesothelial tumors, in contrast to adenocarcinomas of the lung that are tumors of epithelial origin. We studied the expression of N-cadherin, E-cadherin and two cadherinassociated proteins, α-catenin and β-catenin, in 19 pleural mesotheliomas, 16 lung adenocarcinomas and in 2 mesothelioma cell lines using specific monoclonal antibodies and immunohistochemical methods. Our results show that all mesotheliomas express high levels of Ncadherin, regardless of their histological type, in contrast to lung adenocarcinomas which expressed E-cadherin but no N-cadherin. The cadherin-associated proteins, α-catenin and β-catenin, were present in both mesotheliomas and adenocarcinomas. Our results show that pleural mesotheliomas can be distinguished from lung adenocarcinomas based on the differential expression of N-cadherin and E-cadherin, using specific monoclonal antibodies and immunocytochemistry.

Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients

Mesothelial cells that line the peritoneal cavity are capable of producing several proinflammatory cytokines such as interleukin-6 and interleukin-8. Since they are the most numerous cell in the peritoneal cavity when the lining mesothelial cells are included, they may play a major role in the local antibacterial defence mechanism. Cancer antigen (CA)125 is expressed by mesothelial cells (as by other coelomic epithelium-derived cells) and might therefore be considered a marker of the mesothelium. The aim of this study was to determine whether CA125 is a bulk or an activation stage mesothelial cell marker. A positive correlation was found between the mesothelial cell number and the CA125 concentration in dialysate of stable PD patients (P = 0.03). CA125 release by mesothelial cell cultures during confluence showed that the release per cell was constant in time. Stimulation of mesothelial cells in a confluential phase with IL1 beta, TNF alpha, IFN gamma and TGF beta did not result in an increase in CA125 release. Cell lysis showed that CA125 is also present intracellularly. This implies that release of intracellular CA125 can be a disturbing factor in interpreting the CA125 concentration of dialysate in situations where mesothelial cell death may occur, such as in peritonitis. It can be concluded, that our data show that dialysate CA125 is a bulk marker for the mesothelial cell mass in stable PD patients and can thus provide data on the state of the peritoneal membrane in the follow-up of the individual patient.

Cancer Antigen 1251S Locally Produced in the Peritoneal Cavity during Continuous Ambulatory Peritoneal Dialysis

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Localization of plasminogen activator inhibitor‐1 production in inflamed appendix by in situ mRNA hybridization

The peritoneum has been shown to possess fibrinolytic activity which is thought to play a role in the prevention of intra-abdominal adhesion formation. Recently inflamed peritoneal tissue has been shown to have reduced fibrinolytic activity secondary to increased levels of plasminogen activator inhibitor-1 (PAI-1). The aim of this study was to localize the production of PAI-1 in appendix tissue using in situ mRNA hybridization. Sections of normal and inflamed appendix were hybridized with a digoxigenin-labelled cDNA probe. PAI-1 production was localized to both mesothelium and serosal blood vessel endothelium in all inflamed appendix samples. Cell identities were confirmed using immunohistochemistry directed against mesothelial and endothelial cell markers. Staining was not seen on 1 probe following ribonuclease digestion). The identification of the cells expressing the PAI-1 gene in peritoneum increases our understanding of the pathophysiological changes in fibrinolytic activity which occur in inflammation and may lead to adhesion formation.