Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA119597 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT. Methods: 2Ã106 liver cells isolated from Ptenloxp/loxp;Alb-Cre+ mice, expanded from a single CD133+CD45- cell clone, Passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, Passage 1 and 2 (P1 & P2) . Cells were analyzed for gene expression using microarray and real-time PCR. Functional analysis included cell proliferation, migration, and invasion in-vitro and orthotopic tumor growth and metastasis assays in-vivo. Results: Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to the P0 cells, and cells with fibroblastoid morphology. The P2 mesenchymal cells demonstrated increased locomotion on wound healing, increased cell invasion on Matrigel basement membrane, increased EMT associated gene Snail1, Zeb1, and Zeb2 expression, and down-regulated E-cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth compared to P2 Epithelial counterparts, with peritoneal seeding and invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of Hepatocyte Growth Factor (HGF), which acted in paracrine fashion to drive epithelial cells to undergo EMT. Conclusion: EMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in-vivo, which is driven by HGF in a feed-forward mechanism. Total RNA isolated from subcutaneously transplanted tumors with PTENloxp/loxp;Alb-Cre+ genetic background
2010-05-28 | E-GEOD-18255 | biostudies-arrayexpress
Project description:Background: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT. Methods: 2×106 liver cells isolated from Ptenloxp/loxp;Alb-Cre+ mice, expanded from a single CD133+CD45- cell clone, Passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, Passage 1 and 2 (P1 & P2) . Cells were analyzed for gene expression using microarray and real-time PCR. Functional analysis included cell proliferation, migration, and invasion in-vitro and orthotopic tumor growth and metastasis assays in-vivo. Results: Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to the P0 cells, and cells with fibroblastoid morphology. The P2 mesenchymal cells demonstrated increased locomotion on wound healing, increased cell invasion on Matrigel basement membrane, increased EMT associated gene Snail1, Zeb1, and Zeb2 expression, and down-regulated E-cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth compared to P2 Epithelial counterparts, with peritoneal seeding and invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of Hepatocyte Growth Factor (HGF), which acted in paracrine fashion to drive epithelial cells to undergo EMT. Conclusion: EMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in-vivo, which is driven by HGF in a feed-forward mechanism.
2010-05-12 | GSE18255 | GEO
Project description:Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. We show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2+) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites. CdGAP depletion in HER2+ murine primary tumors mediates crosstalk with a Dlc1-RhoA pathway and is associated with a transforming growth factor-β (TGF-β)-induced EMT transcriptional signature. To further delineate the molecular mechanisms underlying the pro-migratory role of CdGAP in breast cancer cells, we searched for CdGAP interactors by performing a proteomic analysis using HEK293 cells overexpressing GFP-CdGAP. We found that CdGAP interacts with the adaptor Talin to modulate focal adhesion dynamics and integrin activation. Moreover, HER2+ breast cancer patients with high CdGAP mRNA expression combined with a high TGF-β-EMT signature are more likely to present lymph node invasion. Our results suggest CdGAP as a candidate therapeutic target for HER2+ metastatic breast cancer by inhibiting TGF-β and Integrin/Talin signaling pathways.
2023-07-14 | PXD043376 | Pride
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT-permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even the partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participates to the primary tumor growth long before the initiation of the invasion-metastasis cascade. arrayCGH profiles analysis of Tert/shp53/Ras epithelial HMEC derivatives and 3 different tumors generated after injection of mesenchymal Tert/shp53/Ras/ HMEC derivatives in fad pads of nude mice
2011-01-11 | E-GEOD-26534 | biostudies-arrayexpress
Project description:Cancer associated fibroblasts (CAFs) are the major cellular component of the tumor microenvironment and they have been shown to stimulate tumor growth, epithelial-to-mesenchymal transition (EMT), invasion and radio-resistance. We used microarrays to investigate the influence of CAFs on the gene expression profile of HNSCC cells in 3D co-cultures
2021-06-15 | GSE178154 | GEO
Project description:Cancer associated fibroblasts (CAFs) are the major cellular component of the tumor microenvironment and they have been shown to stimulate tumor growth, epithelial-to-mesenchymal transition (EMT), invasion and radio-resistance. We used microarrays to investigate the influence of CAFs on the gene expression profile of HNSCC cells in 2D co-cultures
2021-06-15 | GSE178153 | GEO
Project description:An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion (fig. 1). Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.
2020-10-22 | PXD021539 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE39356: MiR-374a Promotes Epithelial-Mesenchymal Transition (EMT) and Metastasis of Breast Cancer (mRNA dataset) GSE39358: MiR-374a Promotes Epithelial-Mesenchymal Transition (EMT) and Metastasis of Breast Cancer (miRNA dataset) Refer to individual Series
2012-07-13 | E-GEOD-39359 | biostudies-arrayexpress
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade. Human mammary epithelial cells (HMEC) were sequentially depleted in p53 through RNA interference (shp53), transduced with H-RasG12V and immortalized by hTert. Two different Tert/shp53/Ras cell population emerge that display either an epithelial (Epi) or a mesenchymal (Mes) phenotype. Gene expression profiles of the Tert/shp53 control cells and of tert/shp53/Ras/Epi and Tert/shp53/Ras/Mes were analyzed.
2012-01-31 | E-GEOD-26541 | biostudies-arrayexpress
Project description:Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. We have engineered the first mouse model of ATC by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion and distant metastases. We have performed expression profiling of thyroids from control, single mutants, compound mutants, follicular tumors from Pten-/- mice, and anaplastic tumors from Pten, p53-/- mice.
2012-03-14 | E-GEOD-30427 | biostudies-arrayexpress