Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA173238 | ENA |
REPOSITORIES: ENA
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Project description:Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. Here, we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Using a genetic mouse model of lung adenocarcinoma, we measured the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of adhesion profiles generated using this platform differentially segregated metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. These interactions appear to be mediated in part by α3β1 integrin both in vitro and in vivo. We show that these galectins also correlate with human disease at both a transcriptional and histological level. Thus, our in vitro platform allowed us to interrogate the interactions of metastatic cells with their surrounding environment, and identified ECM and integrin interactions that could lead to therapeutic targets for metastasis prevention. Cell lines derived from murine lung primary adenocarcinomas and their metastases (Winslow et al., 2011 Nature 473:101-104)
2012-10-11 | E-GEOD-40222 | biostudies-arrayexpress
Project description:Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. Here, we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Using a genetic mouse model of lung adenocarcinoma, we measured the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of adhesion profiles generated using this platform differentially segregated metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. These interactions appear to be mediated in part by α3β1 integrin both in vitro and in vivo. We show that these galectins also correlate with human disease at both a transcriptional and histological level. Thus, our in vitro platform allowed us to interrogate the interactions of metastatic cells with their surrounding environment, and identified ECM and integrin interactions that could lead to therapeutic targets for metastasis prevention.
2012-10-11 | GSE40222 | GEO
Project description:Through promoter capture Hi-C performed directly from patient tissue samples, we report the near-native characterization of intradomain chromatin architecture changes in uterine leiomyomas. This study identifies altered enhancer-promoter interactions and differential enhancer usage of enhancers associated with extracellular matrix-associated genes.
2020-01-01 | GSE128234 | GEO
Project description:TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment. Custom mouse cDNA microarrays were used to measure transcript levels in microdissected anterior prostate tumors from Tmprss2+/+;TRAMP mice, Tmprss2-/-;TRAMP mice or strain-matched benign epithelium. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.
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Project description:Extracellular Matrix Proteolysis by MT1-MMP is Associated with Influenza-Related Mortality
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Project description:This model builds upon two published models focused on the early steps of metastasis by Cohen et al. and on EMT process by Selvaggio et. al. The initial model of Cohen and colleagues was built with two inputs: the ECMenv, which monitored the status of the extracellular matrix, and DNA_damage, which considered DNA alterations that trigger death signals. Four additional inputs were added to account for the presence of Oxygen, growth factors (as GF), TGFbeta and the contact with other neighboring cells (as Neigh). The phenotypes, or outputs of the model include CellCycleArrest, Apoptosis, EMT, ECM_adh (for cell adhesion), ECM_degrad (for cell degradation), Cell_growth (for the dynamics of the tumor growth) and Cell_freeze (for cell motility ability). New genes and pathways include mechanisms around p63 and SRC. Genes from the Hippo pathway and RhoGTPases, such as YAP1, FAK and RAC1 were also inserted to link external signals (i.e., cell–cell contact, stiffness of the extracellular matrix, and stress signals) and intracellular regulation. The resulting network encompasses 45 nodes, with 6 input nodes, representing the possible interactions of an individual cell with external elements, and 8 output nodes or read-outs describing the possible observed phenotypes.
This model was initially developed as a MaBoSS model for a multi-scale model of tumor invasion, developed with PhysiBoSS. As SBML-qual cannot describe fully a MaBoSS model yet, we also include the MaBoSS BND and CFG files.
2023-06-27 | MODEL2304070002 | BioModels
Project description:This study was conducted to investigate the role of MNRR1 in regulating the extracellular matrix and focal adhesion modulating ovarian cancer metastasis
2023-01-15 | GSE218364 | GEO
Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.
2011-12-31 | E-MTAB-583 | biostudies-arrayexpress
Project description:Invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. In this study we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression and methylation profiles of classified aggressive primary uterine adenocarcinomas and leiomyosarcomas.
2021-06-28 | GSE171142 | GEO
Project description:Invasive tumor front (ITF, the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (uADC) and leiomyosarcomas (uLMS).
2021-04-15 | GSE172043 | GEO