Extracellular vesicles promote activation of pro-inflammatory cancer-associated fibroblast in oral cancer
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ABSTRACT:
PROVIDER: PRJNA976919 | ENA |
REPOSITORIES: ENA
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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:To further investigate the molecular mechanisms by which EVs mediated the abnormal localization of tight junction proteins and adherence junction protein, we performed miRNA microarray analysis of extracellular vesicles isolated from breast cancer cells. miRNA expression in extracellular vesicles was collected from MDA-MB-231-D3H1, MDA-MB-231-D3H2LN, BMD2a and BMD2b breast cancer cell lines.
2015-04-02 | E-GEOD-63445 | biostudies-arrayexpress
Project description:Human Fibroblast-Like Synoviocytes Derived Extracellular Vesicles miRNA sequencing
| PRJNA770359 | ENA
Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal chronic lung disease characterized by aberrant intercellular communication, extracellular matrix deposition and destruction of functional lung tissue. While extracellular vesicles (EVs) accumulate in the IPF lung, their cargo and biological effects remain unclear. We interrogated the proteome of EV and non-EV fractions during pulmonary fibrosis and characterize their contribution to fibrosis. EVs accumulated 14 days post-bleomycin challenge, correlating with decreased lung function and initiated fibrogenesis in healthy precision-cut lung slices. Label-free proteomics of broncho-alveolar lavage fluid (BALF)-EVs collected from mice challenged with bleomycin or control identified 107 proteins enriched in fibrotic vesicles. Multiomic analysis revealed fibroblasts as a major cellular source of BALF-EV cargo, which was enriched in Secreted Frizzled Related Protein 1 (SFRP1). Sfrp1 deficiency inhibited the activity of fibroblast-derived EVs to potentiate lung fibrosis in vivo. SFRP1 led to increased transitional cell markers, such as Krt8, and WNT/β-catenin signaling in primary alveolar type 2 cells. SFRP1 is expressed within the IPF lung and localized at the surface of EVs from patient-derived fibroblasts and BALF. Our work reveals altered EV protein cargo in fibrotic EVs promoting fibrogenesis and identifies fibroblast derived vesicular SFRP1 as fibrotic mediator and potential therapeutic target for IPF.
2024-11-05 | GSE272679 | GEO
Project description:In arthritis, synovial fibroblast (SF) senescence is linked to the activation of a pro-inflammatory phenotype contributing to chronic arthritis pathogenesis. Additionally, senescent cells accumulate in ageing tissues further promoting ageing and inflammation. These cells have dysregulated mitochondrial function and metabolism, limited tissue regeneration, produce reactive oxygen species (ROS) and secrete bioactive molecules, including pro-inflammatory cytokines, chemokines and matrix-remodelling enzymes known as SASP (senescence-associated secretory phenotype). In vitro, senescent cells can induce a senescent phenotype in surrounding bystander cells. Interestingly, extracellular vesicles (EVs) have critical roles in cellular senescence and ageing and are mediators in intercellular communication. We hypothesize that senescent cells in osteoarthritic SFs induce senescence and/or a proinflammatory phenotype in non-senescent osteoarthritic SFs, mediated through EV cargo.
2022-10-15 | PXD032757 | Pride
Project description:Fibroblast-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis
| PRJNA1137949 | ENA
Project description:IMP1/IGF2BP1 enters extracellular vesicles in colorectal cancer
2022-09-30 | GSE198804 | GEO
Project description:Background: There is some evidence demonstrating the effect of psychological interventions in improvements in health biological parameters. To best of our knowledge, no study had addressed the impact of any psychological intervention on extracellular vesicles. In addition, Mindfulness-Based Cognitive Therapy (MBCT) and Emotion Focused Therapy for Cancer Recovery (EFT-CR) in the group have never been explored regarding extracellular vesicles and the effectiveness of these was not compared yet.
Objectives:
1. To explore and compare the effect of MBCT and EFT-CR on biological parameters and psychological variables in distressed people who have had breast, prostate and colorectal cancer;
2. In addition, we will explore the acceptability through recruitment and retention rates of MBCT and EFT-CR in group and evaluate whether these interventions are appropriate for a larger clinical trial.
Methods: The design of this study is a parallel randomized controlled trial. Participants will be randomized into MBCT, EFT-CR or usual care. Outcome measures will be assessed before, at the end of the intervention (8 weeks) and follow-ups (24 and 52 weeks from the baseline moment).
Hypotheses: The researchers expected that both interventions will have an effect on extracellular vesicles and other study biomarkers as well as improvements in psychological outcomes, compared to treatment as usual (TAU) group. Regarding the comparative effectiveness, we did not have evidence to hypothesize which one of the interventions will be superior in both biological (extracellular vesicles) and psychological outcomes.
Contribution for practice: The results of this preliminary study would permit to know if there are benefits of these psychological interventions on changes in extracellular vesicles and on psychological outcomes related to health. In addition, this study will permit to determine the acceptability of conducting a larger randomized controlled trial.
| 2332322 | ecrin-mdr-crc
Project description:Most cancer-related deaths are caused by distant metastases, which are tumour cells that have escaped from a primary tumour and passed into the bloodstream to colonize a new organ. In this context, communication between tumour and stromal cells is essential. Indeed, tumor cells interact with cells in the tumor microenvironment and are able to modify them to their advantage. Both extracellular vesicles (EVs) and exosomes are heterogeneous populations of small vesicles present in the tumor microenvironment and in body fluids that have recently emerged as powerful mediators involved in this communication and their transport in fluids. Tumor cells release large quantities of exosomes containing tumor markers, which can then spread to distant locations.
The exosomes are of endosomal origin. They are composed of proteins, lipids, RNA and DNA, and they circulate in the bloodstream. They can be internalized by specific distant cells and thus deliver a functional message. It has recently been shown that tumor exosomes containing pro-metastatic factors form pre-metastatic niches, before the tumor cells actually arrive, while determining the metastatic organotropism of tumors. These properties are now opening up new avenues of research in tumor biomarkers. In recent years, several studies have highlighted different markers contained specifically in exosomes derived from cancer cells. Consequently, exosomes are considered as potential reservoirs of tumor biomarkers that could be clinically useful for the non-invasive diagnosis of cancer, with the advantage of being performed by liquid biopsy. The study of microRNA (miRNA) is of particular interest. Indeed, miRNAs are small non-coding RNAs (between 21 and 25 nucleotides) involved in the regulation of gene expression and which are frequently deregulated in cancer. Several studies underline that the variation of free miRNAs in the blood is correlated with the progression of the disease, particularly in colon cancer. However, the stability of free miRNAs is controversial. Therefore, exosomes represent a very advantageous means of transporting miRNAs in the blood, as they are able to protect miRNAs from degradation by RNAase.
The hypothesis of the project is that circulating exosomes derived from tumours contain markers including specific miRNAs that could be used as biomarkers of early prognosis (survival and progression), easily measured in blood samples from patients with colon cancer. But other molecules contained in exosomes could also be of interest.
| 2349603 | ecrin-mdr-crc
Project description:Cancer-associated fibroblast (CAF) promote immune suppression in the tumor microenvironment by polarizing monocytes to myeloid-derived suppressor cells (MDSC) that potently suppress T-cell function. Using a patient-derived coculture system, we found that extracellular vesicles (EV) released by CAF-induced MDSC directly suppress T-cell proliferation. In this study, we profiled the protein cargo of the EVs isolated from CAF-MDSC and compared to related cell types.
2024-01-03 | PXD035248 | Pride