Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA169161 | ENA |
REPOSITORIES: ENA
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Project description:The increased α-smooth muscle-actin positive cancer-associated fibroblastic cells (CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients We developed a novel 3-D organotypic culture model by co-culturing α-SMA positive CAF and cholangiocarcinoma cells in a collagen matrix.
2012-06-23 | GSE38889 | GEO
Project description:The increased M-NM-1-smooth muscle-actin positive cancer-associated fibroblastic cells (CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients We developed a novel 3-D organotypic culture model by co-culturing M-NM-1-SMA positive CAF and cholangiocarcinoma cells in a collagen matrix. Cholangiocarcinoma cell lines were established by isolating M-NM-1-SMA positive cancer-associated fibroblastic cells (CAF) (BDEsp-TDFE4) and cholangiocarcinoma cells (BDEsp-TDEH10) from tumors arising from bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells). These tumor-derived cells lines were then grown in a rat tail type I collagen gel matrix, alone or in co-culture, and their gene expression profile were compared.
2012-06-22 | E-GEOD-38889 | biostudies-arrayexpress
Project description:SCC12 cells were seeded ontop of organotypic gels with HN-CAF (head and neck carcinoma associated fibroblasts). Differential gene expression was analysed between cancer cells not exposed to CAFs or non-invading cancer cells exposed to CAFs. Squamous cell cancer organotypics were constructed by embedding CAFs in collagen Matrigel matrix with SCC 12cells added on top. Gene expression was compared between non-invaded cancer cells and cancer cells not expoesd to CAFs.
2013-03-23 | E-GEOD-36776 | biostudies-arrayexpress
Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls. comparison 1: CAF co-cultured with OSCC vs. mono-cultured CAF comparison 2: OSCC co-cultured with CAF vs. mono-cultured OSCC 1.7X10(5) YD-10B OSCC cells and 1.7X10(5) CAF were seeded in the upper chamber and lower chamber, respectively, of 6-transwell plates containing collagen-coated 1 micrometer pore transmembrane filters (Becton Dickinson, Franklin Lakes, NJ, USA). Monoculture control samples were generated by culturing only CAF or OSCC on the same side of the filter as in the co-culture design.
2010-06-21 | E-GEOD-18532 | biostudies-arrayexpress
Project description:Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment (TME), serving diverse functions in tumour progression, invasion, matrix remodelling and resistance to therapy. Extensive molecular characterization revealed an increased heterogeneity in the CAF compartment and proposed an interaction between CAFs and tumour-infiltrating immune cells, which may shape tumour immune evasion. However, the precise mechanisms via which CAFs imprint on anti-tumour immunity remain poorly understood. Herein, we describe a synapse formation between α-SMA+ CAFs and regulatory T cells (Tregs) in the TME. Specifically, Foxp3+ Tregs were localized close to α-SMA+ CAFs in diverse types of tumour models as well as in biopsies from melanoma and colorectal cancer patients. Notably, α-SMA+ CAFs demonstrated the ability to phagocytose and process tumour antigens and exhibited a tolerogenic phenotype which instructed a Treg cell movement arrest with Treg cell activation and proliferation, in an antigen-specific manner. Of interest, α-SMA+ CAFs were characterized by the presence of double-membrane structures, resembling autophagosomes, in their cytoplasm, while analysis of single-cell transcriptomic data pointed autophagy and antigen processing/presentation pathways to be enriched in α-SMA-expressing CAF clusters. In a mechanistic view, conditional knockout of the autophagy pathway in α-SMA+ CAFs promoted an inflammatory re-programming of CAFs, reduced Treg cell infiltration, attenuated tumour development, and potentiated the efficacy of immune checkpoint inhibitor immunotherapy. Overall, our findings reveal an immunosuppressive mechanism operating in the TME, which entails the formation of synapses between α-SMA+ CAFs and Tregs in an autophagy-dependent fashion and raises the potential for the development of CAF-targeted therapies in cancer. Here we submit the secretome proteomic analyses.
2024-05-08 | PXD047038 | Pride
Project description:Aim: Differentiation of cardiac fibroblasts (Fb) into myofibroblasts (MyoFb) is responsible for connective tissue buildup in myocardial remodeling. We examined reversibility of MyoFb differentiation. Methods and Results: Adult rat cardiac Fb were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different Fb phenotypes. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fiber formation decorated with alpha-smooth muscle actin (α-SMA). Transforming growth factor-β1 (TGF-β1) promoted terminal differentiation into α-SMA positive MyoFb showing near absence of proliferation i.e. non-p-MyoFb (2-fold increase in cell number after 12 days vs 11-fold for p-MyoFb). SD-208, a TGF-β-receptor-I kinase blocker, inhibited p-MyoFb differentiation as shown by stress fiber absence, low levels of α-SMA protein expression, and high levels of proliferation (32-fold increase after 12 days). Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and 4-fold contraction. Fb produced low levels of collagen and secreted high levels of IL-10. Non-p-MyoFb showed high collagen production and high MCP-1 and TIMP-1 secretion. Transcriptome analysis indicated differential gene expression between all phenotypes. Dedifferentiation of p-MyoFb, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress, shown by stress fiber de-polymerization in 30% of p-MyoFb vs in 8% of non-p-MyoFb. Stress fiber de-polymerization could be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2 day culture in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D culture. Conclusions: Both reduction in mechanical strain and TGF-β-receptor-I kinase inhibition can reverse p-MyoFb differentiation but not in non-p-MyoFb.
2014-01-07 | GSE51824 | GEO
Project description:Angiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture. We used microarrys to examine the effects of TNF-alpha on gene expression in both fibrin and collagen gels during the first 48 hours or culture. Rat aortic rings were cultured in either collagen or fibrin maticies. Half of the cultures from each matrix group were treated with 10ng/ml recombinant rat TNF-alpha, and half were left untreated. These cultures were used to prepare total RNA
2011-07-20 | E-GEOD-23153 | biostudies-arrayexpress
Project description:To more closely reproduce key cellular and stromal features of the desmoplastic reaction of cholangiocarcinoma in vitro, we developed a novel 3-dimensional culture modeling of cancer and stromal cells as a strategy for targeted therapies Cellular, molecular, and functional characterization of different cancer-associated fibroblastic (CAF) and cholangiocarcinoma cell strains isolated from orthotopic tumors arising from bile duct inoculation of spontaneously-transformed rat cholangiocytes (BDEsp cells) in Fischer 344 young adult male rats.
2016-05-31 | E-GEOD-70587 | biostudies-arrayexpress
Project description:Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. While gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and non-tumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1 and Wnt-5A, while re-expression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin- 1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall our findings demonstrate that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts. 16 samples
2012-05-15 | E-GEOD-37738 | biostudies-arrayexpress
Project description:The present study aimed at proposing a novel chemically-induced cirrhosis-associated rat hepatocarcinogenesis model, involving the characterization of histological, biochemical and molecular features. Male Wistar rats received a single dose of diethylnitrosamine (DEN, 200 mg/Kg body weight [b.wt.]), and were submitted to several cycles of thioacetamide (TAA, 200 mg/Kg b.wt.), during 23 weeks. Blood and liver were collected from untreated and DEN/TAA-treated groups. Liver samples were processed for global gene expression (cDNA microarray), histopathological (HE) and collagen content (picrosirius red) evaluations, immunohistochemical (Ki-67, GST-P and α-SMA), biochemical (catalase, glutathione peroxidase and glutathione-S-transferase) and gelatin zymography (MMP-2 and 9) analysis. Using a very stringent analysis (FDR<0.01 and fold change>3), gene expression array evidenced 359 differentially expressed genes upon DEN/TAA regimen. Gene Ontology and functional analyses showed several upregulated genes involved in extracellular matrix organization, mainly collagen type I α1 and 2 (Col1α1, Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 (Timp1 and Timp2) genes. In addition, glutathione S-transferase, pi 1 and 2 (Gstp1 and Gstp2) genes were markedly upregulated. In contrast, functional analyses also revealed the downregulation of antioxidant response genes, as catalase, glutathione peroxidase 1 and glutathione S-transferase mu type 3 (Cat, Gpx1 and Gstm3). In agreement with gene expression data, our model presented extensive liver cirrhosis with increased α-SMA expression and collagen deposition, as well as marked development of preneoplastic GST-P positive hyperplastic lesions and some neoplasms. Besides, we observed a decrease in total glutathione peroxidase, total glutatione-S-tranferase and catalase activities. The characterization of a suitable cirrhosis-associated hepatocarcinogenesis model could provide insights into molecular characteristics of the human disease and be applied to evaluate potential preventive and therapeutic approaches.
2017-10-12 | GSE97083 | GEO