Genome wide analysis of skin cancer cell gene expresison exposed to stromal cancer associated fibroblasts in 3D gel matrix
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36776 | GEO | 2013/03/23
SECONDARY ACCESSION(S): PRJNA156913
REPOSITORIES: GEO
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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:Capan1 (well differentiated pancreatic cancer cell line) was co-cultured with pancreatic stellate cell line (PS1) embedded in a 3D organotypic model and gene expression was analysed in comparison to cancer cells cultured alone without stellate cells. Pancreatic stellate cells were embedded within a gel matrix composing collagen type I and Matrigel, and cancer cells were seeded on top. The gel was lifted on to metal grid after 24 hour and fed from below. Gels were harvested on day 10 and frozen sections obtained. The cancer cell layer on top of the gel was captured by laser microdissection for RNA extraction.
2013-03-23 | E-GEOD-36775 | biostudies-arrayexpress
Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.
2021-08-10 | PXD022635 | Pride
Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.
2021-04-20 | GSE161761 | GEO
Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.
2021-04-20 | GSE161760 | GEO
Project description:Purpose Cancer-associated fibroblasts (CAFs) are a key component of tumors. We aimed to profile the proteome of cancer cell lines representing three common cancer types (lung, colorectal and pancreatic) and a representative CAF cell line from each tumor type to gain insight into CAF function and identify new CAF biomarkers. Experimental Design We used isobaric labeling, liquid chromatography and mass spectrometry to evaluate the proteome of 9 cancer and 3 CAF cell lines. Functions of selected differentially expressed proteins in CAF cell lines were further investigated using siRNA and the expression levels of candidate novel CAF biomarkers were evaluated by immunohistochemistry in 30 human tumor specimens. Results Of the 9460 proteins evaluated, functional enrichment analysis revealed N-glycan biosynthesis and extracellular membrane proteins to be upregulated in CAFs and not in cancer cells. 85 proteins had 16-fold higher expression in CAFs compared to cancer cells. These included previously known CAF markers like ACTA2, FAP and SDC2. Novel biomarkers overexpressed in CAFs were noted, including HSPB6 and PTGS1. SiRNA knockdown of these genes encoding these proteins did not reduce contractility in lung CAFs, suggesting they were not crucial to this function despite high expression. Immunohistochemical analysis of 30 tumor samples (10 lung, 10 colorectal and 10 pancreatic) showed HSPB6 and PTGS1 expression were restricted to the stroma. Conclusions An unbiased analysis of the differences in the proteome of cancer cells compared to CAFs revealed increased expression of HSPB6 and PTGS1 in CAFs.
2023-08-21 | PXD040360 | Pride
Project description:2 Breast Cancer Cell lines were seeded onto TCPS, on 2D PEG-PC gels, and encapsulated in 3D PEG-Maleimide gels as single cells or spheroids to determine transcript level changes based on culture platform
2017-03-01 | GSE93562 | GEO
Project description:Carcinoma-associated fibroblasts (CAFs) that express ?-smooth-muscle-actin (?SMA+) contribute to cancer progression, but their precise origin and role in tumorigenesis is not established. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow and derive from mesenchymal stem cells (MSCs). Surprisingly, we find that ?SMA+ myofibroblasts (MF) are niche cells normally present in bone marrow and increase markedly in the bone marrow and blood during progression to dysplasia. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5? and BMP4 and show DNA hypomethylation. Bone marrow (BM)-derived CAFs strongly promote tumor growth in organotypic and xenograft models. In addition, CAFs are generated from MSCs and are recruited to distant tumor sites in a TGF-?- and SDF-1?-dependent manner. Carcinogenesis therefore involves the expansion and relocation of normal bone marrow niche cells to the tumor site where they create a new niche to sustain cancer progression. Since resident (non-BM-derived) CAFs could not be cultured and directly compared to BM-derived CAFs, we additionally isolated total RFP(+) gastric CAFs from aSMA-RFP mice with Helicobacter felis-induced dysplasia, and compared them to GFP(+) BM-derived gastric CAFs from mice with H. felis-induced dysplasia mice that had been transplanted with UBC-EGFP bone marrow. The RFP+ CAFs (HF CAF) represent total CAFs (of which only 20% were BM-derived), while the latter represented only BM-derived CAFs (BM CAF). We compared their gene expression using the Illumina array (MouseWG-6v2) directly after FACS sorting. Interestingly, the GFP+ BM-derived CAFs expressed higher levels of inflammatory genes (IL-6, IL-1?, IL-33) and a number of tumor and stem cell associated factors (CCL5, SPP1, Notch3, MMP9, CD47, CXCR4, PARP10,) compared to the total (RFP+) population of gastric CAFs. Comparison of bone marrow-derived GFP-labeled gastric CAFs versus all gastric CAFs.
2010-10-01 | E-GEOD-23548 | biostudies-arrayexpress
Project description:Intratumoral hypoxia causes the formation of dysfunctional blood vessels which contribute to tumor metastasis. Blood vessels are embedded in the tumor stroma where cancer-associated fibroblasts (CAFs) constitute the most prominent cellular component. We found that hypoxic human mammary CAFs promote blood vessel growth in CAF-endothelial cell co-cultures in vitro. Mass spectrometry-based proteomic analysis of CAF secretome unravels how hypoxic CAFs contribute to blood vessel abnormalities by altering the secretion of a multitude of pro- and anti-angiogenic factors. Hypoxia induces pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Our study provides a map of unprecedented depth of hypoxia-induced molecular alterations in mammary CAFs that can be exploited to identify novel mechanisms that control hypoxic CAF functions.
2019-02-15 | PXD006535 | Pride
Project description:Global gene expression of Synechocystis sp. PCC 6803 encapsulated in silica gel was examined by microarray analysis. Cultures were encapsulated in gels derived from aqueous precursors and gels derived from alkoxide precursors and incubated under constant light for 24 hours prior to RNA extraction. Cultures suspended in liquid media were also exposed to 500 mM salt stress and incubated under identical conditions, for comparison purposes. The expression of 414 genes was significantly altered by encapsulation in aqueous-derived gels (fold change >/= 1.5 and P-value < 0.01), the expression of 1143 genes were significantly altered by encapsulation in alkoxide derived gels, and only 243 genes were common to both encapsulation chemistries. Additional qRT-PCR analyses of four select genes; ggpS, cpcG2, slr5055, and sll5057, confirmed microarray results. These results illustrate that encapsulation stress is quite different than salt stress in terms of gene expression response. Furthermore, a number of hypothetical and unknown proteins associated with encapsulation and alcohol stress have been identified, with implications for improving encapsulation protocols and rationally engineering microorganisms for direct biofuel production.
2012-04-24 | GSE37482 | GEO