Differential susceptibility of human pleural and peritoneal mesothelial cells to asbestos exposure
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63966 | GEO | 2015/03/02
SECONDARY ACCESSION(S): PRJNA269624
REPOSITORIES: GEO
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Project description:We hypothesize that the observed differences in incidences of pleural and peritoneal malignant mesothelioma (MM) are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis, we characterized cellular responses to asbestos in a controlled environment using high-throughput RNA sequence and other assays. Examination of asbestos-treated versus untreated mesothelial cells from four cell lines representing two tissue types in culture.
2015-03-02 | E-GEOD-63966 | biostudies-arrayexpress
Project description:Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. But studies in rodents showed that certain multiwalled carbon nanotubes (MWCNTs) can induce malignant mesotheliomas. This study aimed to understand molecular pathways leading to the development of malignant mesotheliomas induced by MWCNTs and amosite asbestos in Wistar rats. Using Affymetrix microarrays, we carried out genome-wide transcriptome analysis on malignant peritoneal meosotheliomas induced by MWCNTs and amosite asbestos. The transcriptome of MWCNTs and amosite asbestos-induced mesotheliomas exhibited commonalities, but also differences pertaining to differentially-expressed genes (DEGs), regulated canonical pathways, and molecular functions.
2024-02-01 | GSE233803 | GEO
Project description:Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that sub-chronic exposure (4 month) to single- and multi-walled CNTs induced proliferation, migration and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome expression microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study provides new evidence for CNT-induced cell invasion and indicates the role of MMP-2 in the process. Whole genome expression profiling was conducted on human immortalized pleural mesothelial cells (MeT5A) following 4 month in vitro sub-chronic exposure to six separate treatments to assess differences in carbon nanotube (CNT) vs. asbestos potential tumorigenesis signaling. Dispersed single wall CNT (D-SWCNT), multi-wall CNT (D-MWCNT), crocidolite asbestos (ASB) and saline (SAL) exposed cells were compared to Survanta® dispersant (DISP) passage control cells. DISP and SAL cells served as control treatments for CNT- and ASB-exposed cells, respectively. Each treatment possessed 3 biological cDNA replicates. One technical replicate was performed per biological sample.
2015-11-23 | E-GEOD-48855 | biostudies-arrayexpress
Project description:Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that sub-chronic exposure (4 month) to single- and multi-walled CNTs induced proliferation, migration and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome expression microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study provides new evidence for CNT-induced cell invasion and indicates the role of MMP-2 in the process.
2015-11-23 | GSE48855 | GEO
Project description:Exposure to asbestos fibres causes profound pathological changes in the pleural cavity and can result in the development of a fatal tumour, malignant mesothelioma (MM). Due to their structural similarities there is concern that carbon nanotubes (CNTs) may present a similar inhalation hazard. However the underlying mechanisms leading to fibre-mediated mesothelioma development are not yet fully understood. To investigate the molecular changes which occur at the mesothelium as a consequence of direct exposure to fibres, short and long asbestos fibres (SFA and LFA) and short and long CNTs (NTS and NTL) were instilled directly into the pleural cavity in mice. After 12 weeks RNA was extracted from the diaphragm and microarray analysis was performed on all of the treatment groups compared to a 0.5% BSA/saline control. Concurrent histopatholgical investigations were performed and revealed that exposure to fibres resulted in responses that were dependent upon the length of the fibres, but not on fibre type. In response to NTL and LFA there was acute inflammation and fibrosis on the parietal pleura; no inflammatory changes were detected histologically after exposure to SFA and NTS. Furthermore, changes in the mTOR signalling pathway were observed. Thus, this study served to illustrate which pathways are involved in the development of fibre-mediated toxicity, and demonstrated that pleural lesions induced by long asbestos fibres and long CNT exhibit a common pro-oncogenic molecular signature.
2017-11-20 | GSE51636 | GEO
Project description:Malignant mesothelioma (MM) is an aggressive cancer of mesothelial cells of pleural and peritoneal cavities. In 85% of cases both pleural and peritoneal MM is caused by asbestos exposure. Although both are asbestos-induced cancers, the incidence of pleural MM is significantly higher (85%) than peritoneal MM (15%). It has been proposed that carcinogenesis is a result of asbestos-induced inflammation but it is not clear what contributes to the differences observed between incidences of these two cancers. We hypothesize that the observed differences in incidences of pleural and peritoneal MM are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis we characterized cellular responses to asbestos in a controlled environment. We found significantly greater changes in genome-wide expression in response to asbestos exposure in pleural mesothelial cells as compared to peritoneal mesothelial cells. In particular, a greater response in many common genes (IL-8, ATF3, CXCL2, CXCL3, IL-6, GOS2) was seen in pleural mesothelial cells as compared to peritoneal mesothelial cells. Unique genes expressed in pleural mesothelial cells were mainly pro-inflammatory (G-CSF, IL-1?, IL-1?, GREM1) and have previously been shown to be involved in development of MM. Our results are consistent with the hypothesis that differences in incidences of pleural and peritoneal MM upon exposure to asbestos are the result of differences in mesothelial cell physiology that lead to differences in the inflammatory response, which leads to cancer.
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Project description:Human malignant mesothelioma (MM) is an aggressive tumor strongly associated with asbestos exposure. SM patients generally have poorer prognosis compared to EM patients. To identify potential genes accounting for the differential prognosis between these two subtypes, we compared the microarray gene expression profiles of rat SM and EM tissues induced by intraperitoneal injections of 3 types of asbestos (chrysotile,crocidolite and amosite). Carcinogenesis protocol was performed using specific pathogen-free male and female F1 hybrid rats between Fischer344 and Brown-Norway strains. A total of 28 microarrays (Whole Rat Genome Microarray) were used for screening purpose: The 2 arrays were used for knife-scraped peritoneal mesothelial cells, 2 arrays for cultured peritoneal mesothelial cells and 24 arrays for MM samples.
2014-06-04 | E-GEOD-48298 | biostudies-arrayexpress
Project description:We screened pleural effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass spectrometry-(MS-) based proteomics using isobaric tags for relative and absolute quantification (iTRAQ) and used narrow range immobilized pH gradient/high resolution isoelectric focusing (IPG/HiRIEF; pH 4 to 4.25) prior to analysis by nano liquid chromatography-coupled MS/MS. Pleural effusions from patients with malignant mesothelioma (n=6), lung adenocarcinoma (n=6), or benign mesotheliosis (n=7) were analyzed, and more than 1,300 proteins were identified.
2014-01-14 | PXD000531 | Pride
Project description:Malignant mesothelioma is an aggressive tumour arising from the mesothelial cells lining the pleura, peritoneum or pericardium. The principal carcinogen associated with malignant mesothelioma is asbestos . A transgenic mouse model, denoted MexTAg, which encodes the Simian Virus 40 (SV40) large T antigen (TAg) downstream of the mesothelin promoter was developed. Inactivation of the tumour suppressors p53 and RB following binding to TAg results. In this model mesothelioma develops in the mesothelial cell compartment after the mice have been exposed to asbestos. The MexTAg transgenic mouse model of mesothelioma model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out.
2016-01-30 | E-MTAB-3988 | biostudies-arrayexpress
Project description:Diagnosis of malignant pleural mesothelioma (MPM) is difficult, the most common differential diagnosis being benign pleural diseases and metastatic adenocarcinomas. In order to identify novel markers able to improve diagnostic accuracy, we performed a genome-wide gene expression analysis on tumor cells lines established from pleural effusions (13 MPM and 4 lung adenocarcinoma). Our microarray analysis led to the identification of genes encoding novel cellular and soluble markers whose expression was validated by RT-qPCR. Immunohistochemical staining of tumor biopsies with anti-type-III collagen antibodies were positive in mesothelioma cells but not in adenocarcinoma cells. Using ELISA, we showed that the C-C motif chemokine 2 (CCL2) concentration was significantly higher in pleural effusions from patients with mesothelioma (n = 61) than in subjects with adenocarcinoma (n = 25) or with benign pleural effusions (n = 15): median (interquartile range) = 2.99 ng/mL (1.76-6.01) versus 0.99 ng/mL (0.51-1.83) and 1.47 ng/mL (0.80-1.56), respectively, P < 0.0001. Conversely, the galectin-3 concentration was lower in mesothelioma: 11.50 ng/mL (6.73-23.53) versus 24.74 ng/mL (20.42-70.35) and 17.64 ng/mL (14.81-24.68), respectively, P < 0.0001. The AUC for CCL2 were 0.8030 and 0.7716 for differentiating mesothelioma from adenocarcinoma or benign effusions, respectively. Similarly, the AUC obtained for galectin-3 were 0.7980 and 0.6923, respectively. In conclusion, type-III collagen, CCL2 and galectin-3 are promising new diagnostic markers for mesothelioma.
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