ACSL5 Mediates Adaptation to the Palmitic Acid-Enriched Pulmonary Microenvironment to Enhance Metastatic Breast Cancer Cell Survival and Lung Metastasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE314334 | GEO | 2026/01/09
REPOSITORIES: GEO
Similar Datasets
Project description:Metastasis accounts for 90% of cancer-related death. Distant metastasis follows a non-random pattern, termed “organotropism”. The lung is a common site for BC metastasis, yet the underlying mechanisms and treatment strategies for lung metastasis remain unclear.
2026-01-09 | GSE314450 | GEO
Project description:Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis. Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes
2015-06-17 | E-GEOD-68919 | biostudies-arrayexpress
Project description:Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis.
2015-06-17 | GSE68919 | GEO
Project description:LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the regulatory mechanisms of lung metastasis in breast cancer, we analyzed the chromatin structure of MDA-MB-231 and LM2-4175 cell lines.
2019-07-31 | GSE124379 | GEO
Project description:LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the melecular mechanisms of lung metastasis in breast cancer,we analyzed the RNA-seq data of MDA-MB-231 and LM2-4175 cell lines.
2019-07-31 | GSE124380 | GEO
Project description:Bone is the most frequent site of metastases from breast cancer (BC), although no biomarkers are yet available to predict the risk of skeletal dissemination. Here, we attempted to identify a gene signature correlated with bone metastasis (BM) onset in circulating tumor cells (CTCs) isolated from 40 metastatic BC patients, grouped according to their metastasis sites at the time of enrollment, namely “BM” (bone-only), “ES” (extra-skeletal) or “BM+ES” (bone and extra-skeletal). A 134-gene panel, derived from an extensive literature review, was validated on sub-clones of the MDA-MB-231 BC cell line with variable organotropism and then applied to CTC groups for targeted RNA sequencing. No correlation was found between CTC number and clinico-pathologic variables, whereas 31 differentially expressed genes emerged from “BM” and “ES” CTC comparison. The putative prognostic meaning of the “top-10” most deregulated genes was finally explored and pointed out by employing an external BC dataset.
2020-10-29 | GSE160314 | GEO
Project description:While primary breast cancer (BC) is often effectively managed, metastasis remains the primary cause of BC-related fatalities. Gaps persist in our understanding of the mechanisms underlying cancer cell predilection for specific organs (organotropism). Unraveling these mediators of site-specific metastasis could enhance early detection and enable more tailored interventions. Liquid biopsy represents an innovative diagnostic approach in cancer involving the non-invasive analysis of biological materials found in body fluids like blood or urine. These materials include circulating tumor cells, cell-free circulating tumor DNA, and tumor-derived extracellular vesicles (EVs), which offer valuable insights for characterizing and monitoring tumor genomes to advance personalized medicine. EVs, lipid-bound particles released from cells into the extracellular space, facilitate intercellular communication by transporting proteins and DNA (EV-DNA) implicated in cancer progression and organ-specific metastasis. The aim of this study was to conduct an in-depth analysis of cell-free DNA (cfDNA) and EVs using a murine model of BC cell lines with distinct metastatic potentials and organotropisms (lung, bone, liver, brain). We characterized the secretome of 8 different metastatic cell lines originating from the same parental non metastatic and metastatic cell line, as well as normal mammary epithelial cells to identify unique biomarkers specific to metastatic sites. Using ultracentrifigcation, we isolated small EVs ranging from 78.9 to 101nm isolated from the conditioned media of the cell lines. We confirmed the presence of established EV markers, including CD81, TSG101 and syntenin. Transmission electron microscopy revealed interesting EV secretion patterns that differed according to cell line. We demonstrated the presence of EV-DNA and cfDNA in all the cell lines, with varying concentrations. We also found that a common BC mutation in TP53 can be specifically detected in both EV-DNA and cfDNA of cancer cell cultures using droplet digital PCR. The proteomic characterization of EVs through high throughput mass spectrometry revealed common EV signatures and proteins involved in cancer processes and organotropism unique to distinct site-specific cell lines. Specifically, we found enrichment of integrin receptors in metastatic cancer EVs compared to EVs secreted from normal epithelial cells and matched tumorigenic nonmetastatic cell lines. Gene ontology (GO) pathway analysis revealed that cancer derived EVs display a cell adhesion signature and are enriched with proteins involved in extracellular matrix interaction, focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Interestingly, EVs containing heat shock proteins and DNA binding proteins are released by both cancer and normal cells. A total of 460 proteins were quantified with a high confidence level, including 70% of the TOP 200 exosome markers archived by Vesiclepedia. Taken together, we characterized the quantity and cargo of EVs in a unique model of BC organotropism, suggesting that EV-DNA and EVs were informative of normal and cancer states. This work could help to identify BC biomarkers associated with site-specific metastasis as well as new therapeutic targets.
2025-06-02 | PXD055261 | Pride
Project description:Metastasis accounts for most of cancer-related deaths. Paracrine signaling between tumor cells and the stroma induces changes in the tumor microenvironment required for metastasis. Transcription factor c-Myb was associated with breast cancer (BC) progression but its role in metastasis remains unclear. Here we show that increased c-Myb expression in BC cells inhibits spontaneous lung metastasis through impaired tumor cell extravasation. On contrary, BC cells with increased lung metastatic capacity exhibited low c-Myb levels. We identified a specific inflammatory signature, including Ccl2 chemokine; that was expressed in lung metastatic cells but was suppressed in tumor cells with higher c-Myb levels. Tumor cell-derived Ccl2 expression facilitated lung metastasis and rescued trans-endothelial migration of c-Myb overexpressing cells. Clinical data show that the identified inflammatory signature, together with a MYB expression, predicts lung metastasis relapse in BC patients. These results demonstrate that the c-Myb-regulated transcriptional program in BCs results in a blunted inflammatory response and consequently suppresses lung metastasis.
2018-01-01 | GSE104264 | GEO
Project description:Introduction: The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis. Methods: To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors. Results: Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings. Conclusion: In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.
2023-12-03 | GSE248830 | GEO
Project description:Mesenchymal stromal cells were cultured in 3D PEG hydrogels for 7 days in the presence of serum-free media or conditioned media from a panel of breast cancer cells (MCF-7, MDA-MB-231, MDA-MB-231 lung-tropic, MDA-MB-231 brain-tropic, MDA-MB-231 bone-tropic). In all cases, the secretomes were collected after cancer cells were in serum-free media for 24h.
2019-05-28 | E-MTAB-6998 | biostudies-arrayexpress