Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149705 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle, and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer. We produced neural invasion (N-inv) model using intraneural injection of Capan-1 cells to left sciatic nerve of male SCID mouse. For controls, subcutaneous model (SC) and PBS model were produced. Microarray analysis was performed using the first lumbar cord (L1) from PBS, SC, and N-inv mice at 6 w (n = 2 each).
2011-12-07 | E-GEOD-34189 | biostudies-arrayexpress
Project description:Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle, and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer.
2011-12-07 | GSE34189 | GEO
Project description:Perineural invasion (PNI) is a prominent characteristic of pancreatic ductal adenocarcinoma (PDAC) and indicates poor prognosis. The invasion of the surrounding nerves by pancreatic cancer cells not only provides route for metastasis but also contributes to neural remodeling and changes in the neuronal milieu that can profoundly influenced the microenvironment of pancreatic cancer. To investigate the downstream molecules associated with PNI, the experiment analyzed mRNA expression of 50 pairs of pancreatic ductal adenocarcinoma tissue and paired adjacent non-tumor tissue, among which 28 pairs of cases diagnosed with PNI by experienced pathologist. Results provide new insight into molecular basis for the influence of PNI on the microenvironment of pancreatic cancer.
2017-08-04 | GSE102238 | GEO
Project description:Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. Despite its recognized clinical impact, the molecular mechanisms underlying PNI are not well understood. In this study, we isolated perineural invasion-associated cancer-associated fibroblasts (pCAFs), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared to non-perineural invasion-associated CAFs (npCAFs). Utilizing single-cell, high-throughput sequencing, and metabolomics, we identified a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAFs-derived lactate is absorbed by tumor cells, facilitating histone H3K18 lactylation. This epigenetic modification activates the transcription of neural invasion-associated genes such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, correlated with increased enzymatic activity and glycolytic flux. Targeting of GAPDH and lactylation modifications significantly inhibits neural invasion in a KPC mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Our findings provide critical insights into the role of pCAFs in the PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.
2025-03-19 | GSE290654 | GEO
Project description:Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. Despite its recognized clinical impact, the molecular mechanisms underlying PNI are not well understood. In this study, we isolated perineural invasion-associated cancer-associated fibroblasts (pCAFs), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared to non-perineural invasion-associated CAFs (npCAFs). Utilizing single-cell, high-throughput sequencing, and metabolomics, we identified a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAFs-derived lactate is absorbed by tumor cells, facilitating histone H3K18 lactylation. This epigenetic modification activates the transcription of neural invasion-associated genes such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, correlated with increased enzymatic activity and glycolytic flux. Targeting of GAPDH and lactylation modifications significantly inhibits neural invasion in a KPC mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Our findings provide critical insights into the role of pCAFs in the PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.
2025-03-05 | GSE290845 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumour. Factors secreted by tumour cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Among them were GDF15 and VGF, factors involved in cachexia and pain stimuli. GDF15 and VGF promoted CSC self-renewal and growth through autocrine effects. TGFβ/Activin signalling lowered GDF15 and VGF expression via SMAD2/3-SMAD4-SNON, switching to ATF4-CREB-mediated induction upon cell stress. Co-culture of PDAC-CSCs and hESC-derived neural cells for mimicking cellular crosstalk in PDAC revealed that paracrine signalling via GDF15/VGF promoted nociceptor formation and neurite outgrowth. In turn, Substance P from neurons supported CSC self-renewal, EMT/migration and clonal evolution that was also impacted by SMAD4 genetic status. Lastly, the serum levels of GDF15 and VGF were elevated in PDAC patients suggesting their utility as biomarkers for PDAC detection. Collectively, our data uncovered that cachexia and pain signalling factors mediate the crosstalk between CSCs and nociceptors.
2024-04-06 | PXD046026 | Pride
Project description:A variety of mechanotransduction forces are altered in the tumor microenvironment (TME) and these biophysical forces can influence cancer progression. One such force is interstitial fluid flow (IFF) - the movement of fluid through the tissue matrix. IFF was previously shown to induce invasion of cancer cells, but the activated signaling cascades remain poorly understood. Here, it is demonstrated that IFF induces invasion of ERBB2/HER2 expressing breast cancer cells via activation of phosphoinositide-3-kinase (PI3K). In constitutively activate ERBB2 expressing cells that have undergone epithelial-to-mesenchymal transition (EMT), IFF-mediated invasion requires the chemokine receptor CXCR4, a gradient of its ligand CXCL12, and activity of the PI3K catalytic subunits p110a and ?. In wild-type ERBB2 expressing cells, IFF-mediated invasion is chemokine receptor-independent and requires only p110a activation. To test whether cells undergoing EMT alter their signaling response to IFF, TGFb1 was used to induce EMT in wild-type ERBB2-expressing cells resulting in IFF-induced invasion dependent on CXCR4 and p110?. 2 cell lines (NeuN, NeuT), 2 conditions (flow, static), 3 replicates each, 12 samples total
2015-01-06 | E-GEOD-64670 | biostudies-arrayexpress
Project description:Cachexia frequently develops in patients with pancreatic ductal adenocarcinoma (PDAC) and contributes to cancer deaths.Sex differences have been observed in cancer cachexia; however, the underlying molecular mechanisms are far less addressed. We assessed sex difference in PDAC cachexia phenotypes in the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of PDAC and profiled gene expression in the quadriceps skeletal muscles. Males with PDAC experienced earlier cachexia-onset than the female counterpart and activin blockade by ACVR2B/Fc reduced cachexia sympotomes in males but not females. PDAC induced earlier global transcritome alterations in males than females.
2022-05-10 | GSE157251 | GEO
Project description:Cachexia is a systemic metabolic syndrome characterized by loss of fat and skeletal muscle mass in chronic wasting diseases such as cancer. The regulation of cellular protein synthesis in response to workload in skeletal muscle is generally blunted in cancer cachexia; however, the precise molecular regulation is largely unknown. In this study, to examine the molecular mechanism of skeletal muscle protein metabolism in cancer cachexia, we analyzed comprehensive gene expression in skeletal muscle using microarrays. CD2F1 mice (male, 7 weeks old) were subcutaneously transplanted (1*10^6 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Functional overload of the plantaris muscle by synergist ablation was performed at the 2nd week, and the plantaris muscle was sampled at the 4th week of cancer transplantation. The hypertrophy of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mTOR signaling) associated with compensatory overload was significantly suppressed with the cancer cachexia. Gene expression profiling and pathway analysis by microarray showed that resistance to muscle protein synthesis associated with cancer cachexia was induced by downregulation of insulin-like growth factor-1. These observations show that cancer cachexia induces resistance to muscle protein synthesis, which could be a potential factor inhibiting the adaptation of skeletal muscle growth to physical exercise.
2021-10-15 | GSE185934 | GEO