Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis

Hapangama, Dharani; Raju, RS; Valentijn, Anthony; Barraclough, Dong L.; Hart, Anna; Turner, Mark A.; Platt-Higgins, Angela; Barraclough, Roger; Rudland, Philip S.

doi:10.1093/humrep/der412

Cited by 44 publications

(38 citation statements)

References 54 publications

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“…The low number of two groups of samples used for the microarray analysis might limit the microarray results and these patients could have individual differences. Candidate target transcripts need to be validated with more the validated results [30 mRNAs in endometriosis, including S100P [31], TNFSF10 [32], IL-11 [33] These lncRNAs are expressed differently in ectopic, eutopic and normal endometrium. Therefore, study of these lncRNAs in the pathogenesis of endometriosis will be the target of more research.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis

Wang

Yang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Dysregulated long non-coding RNAs (lncRNAs) can lead to the occurrence of various diseases; however, reports of the function of lncRNAs in endometriosis and related studies are scarce. The pathogenesis of endometriosis is still poorly understood. Methods: Dysregulated lncRNAs and mRNAs between eutopic and normal endometrium (both are late secretory) were analyzed by lncRNA microarray. Eight lncRNAs and mRNA CDK6 were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Results: Microarray expression profiling suggests 1277 lncRNAs (488 up- and 789 down-regulated) and 1216 mRNAs (578 up- and 638 down-regulated) were expressed differentially between eutopic and normal endometrium. Pathway analysis and gene ontology (GO) analysis found differently expressed lncRNAs associated with the cell cycle and immune regulation. The relative level of expression of CDK6 and AC002454.1 were obtained by qRT-PCR and the Pearson correlation coefficient was 0.747 (p<0.0001). A coding-noncoding gene co-expression (CNC) network was constructed for these validated lncRNAs. Conclusion: These dysregulated lncRNAs might provide information for new biomarkers or novel therapeutic targets of endometriosis. AC002454.1 might induce cell cycle disorder by regulating CDK6 to participate in the pathogenesis of endometriosis.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis

Wang

Yang

et al. 2015

Cell Physiol Biochem

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“…After pretreatment, sections were incubated with rabbit monoclonal anti-vimentin (clone V9; Ventana, Tucson, AZ, USA; pre-diluted) [26], rabbit monoclonal anti-bone morphogenic protein-2 (clone N/A; Novus Biologicals, Littleton, CO, USA; 1:500 diluted) [27], rabbit monoclonal anti-β2 microglobulin (clone N/A; Dako Denmark A/S, Glostrup Denmark; 1:100 diluted) [28], rabbit monoclonal anti-β-catenin (clone 14; Ventana, Tucson, AZ, USA; pre-diluted) [29] and rabbit monoclonal anti-osteopontin (clone N/A; Novus Biologicals, Littleton, CO, USA; 1:100 diluted) [30] antibodies. Reactions were revealed with an ultraView Universal DAB Detection Kit (Ventana, Tucson, AZ, USA).…”

Section: Methodsmentioning

confidence: 99%

Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics

et al. 2014

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BackgroundMammary microcalcifications have a crucial role in breast cancer detection, but the processes that induce their formation are unknown. Moreover, recent studies have described the occurrence of the epithelial–mesenchymal transition (EMT) in breast cancer, but its role is not defined. In this study, we hypothesized that epithelial cells acquire mesenchymal characteristics and become capable of producing breast microcalcifications.MethodsBreast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN).ResultsThe complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions. Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications.ConclusionsWe found significant differences in the elemental composition of calcifications between benign and malignant lesions. Observations of cell phenotype led us to hypothesize that under specific stimuli, mammary cells, which despite retaining a minimal epithelial phenotype (confirmed by cytokeratin expression), may acquire some mesenchymal characteristics transforming themselves into cells with an osteoblast-like phenotype, and are able to contribute to the production of breast microcalcifications.

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“…Threemicrometer-thick paraffin sections of tumor samples grown on CAM were prepared for immunostaining as previously described. 14 …”

Section: Cell Culturementioning

confidence: 99%

Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide

Parkes

Kamal

Valentijn

et al. 2018

Int J Gynecol Cancer

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Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis

Abstract: We propose that these MIPs enhance endometrial cell invasiveness and contribute to the establishment of ectopic endometriotic deposits after retrograde menstruation.

Cited by 44 publications

References 54 publications

Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis

Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis

Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics

Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide

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