Bulk RNA seq of in vitro co- culture of distinct subtypes of oral cancer associated primary fibroblasts and oral cancer cell line
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE294386 | GEO | 2025/04/11
REPOSITORIES: GEO
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Project description:Heterogeneity in oral cancer associated fibroblasts (CAFs)in tumor microenvironment modulate plasticity of malignant epithelial cells to drive tumorigenesis, ultimately leading to poorer clinical outcome. We identified a receptor tyrosin kinase 'TEK' or Tie2 involved in myofibroblastic differentiation of CAFs. Differentiated CAFs induce stochastic plasticity in oral cancer cells both in stemness and EMT axes. Inhibiting Tie2 in myofibroblastically differentiated CAFs purturbed their cancer cell remodelling ability. Here in this study we performed scRNA seq analysis to understand distinct CAF driven transcriptionl states of cancer cells to undertsand CAF driven cancer cells reprogramming in a higher resolution.
2025-04-21 | GSE295234 | GEO
Project description:Introduction: Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer and has a survival rate of ~50% over five years. New treatment strategies are sorely needed to improve survival rates – and a better understanding of the mechanisms underlying tumorigenesis is needed to develop these strategies. The role of the tumor microenvironment (TME) has increasingly been identified as crucial in tumor progression and metastasis. One of the main constituents of the TME, cancer-associated fibroblasts (CAFs), plays a key role in influencing the biological behavior of tumors. Multiple mechanisms contribute to CAF activation, such as TGFβ signaling, but the role of extracellular vesicles (EVs) in CAF activation in OSCC is poorly understood. Assessing the impact of oral cancer-derived EVs on CAF activation will help to better illuminate OSCC pathophysiology and may drive development of novel treatments options. Materials and Methods: EVs were isolated from OSCC cell lines (Cal 27, SCC-9, SCC-25) using differential centrifugation. Nanoparticle tracking analysis was used for EV quantification and size characterization, and Western blot to confirm the presence of EV protein markers. Oral fibroblasts were co-cultured with enriched EVs, TGFβ, or PBS over 72 hours to assess activation. Flow cytometry was used to evaluate the difference in CAF markers. RNA collected from fibroblasts was extracted and the transcriptome was sequenced. Conditioned media from the co-cultures was evaluated with cytokine array profiling. Results: OSCC-derived EVs can activate oral fibroblasts into CAFs that are different from those activated by TGFβ, suggesting different mechanisms of activation and different functional properties. Gene set enrichment analysis using expression data from activated CAFs showed several upregulated inflammatory pathways in those CAFs exposed to OSCC-derived EVs. Marker genes for inflammatory CAF subtypes were also upregulated. This was not seen in CAFs activated by TGFβ. Finally, cytokine array analysis on secreted proteins from CAFs revealed elevated levels of several pro-inflammatory cytokines from CAFs activated by EVs, for instance IL-8 and CXCL5. Conclusions: Taken together, our results reveal the ability of OSCC-derived EVs to activate fibroblasts into CAFs. These CAFs seem to have unique properties, differing from TGFβ-activated CAFs. Gaining an understanding of the interplay between EVs and stromal cells such as CAFs could lead to further insights into OSCC tumorigenesis and potential novel therapeutics.
2023-09-07 | GSE233618 | GEO
Project description:We identified adipocyte enhancer binding protein 1 (AEBP1) as a novel cancer-associated fibroblast (CAF) marker in oral squamous cell carcinoma (OSCC). To study the function of AEBP1 in CAFs, we knocked down AEBP1 in CAFs isolated from surgically resected primary OSCCs. We found that genes associated with cell cycle were significantly affected by AEBP1 knockdown in CAFs.
2023-09-13 | GSE234220 | 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: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. We used liquid chromatography and tandem 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 studied using siRNA and expression of new CAF biomarkers identified in cell lines were studied by immunohistochemistry in 30 human tumor specimens. 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. An unbiased analysis of the differences in the proteome of cancer cells compared to CAFs revealed increased expression of HSPB6 and PTGS1 in CAFs.
2024-08-22 | PXD054500 | 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.
2021-08-10 | PXD022635 | Pride
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:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
2023-11-10 | GSE218214 | GEO
Project description:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
2023-11-10 | GSE218204 | GEO
Project description:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
2023-11-10 | GSE218198 | GEO