Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing of tumor-associated macrophages from Gpr65-wild-type and -knockout C57BL/6J mice fed with high-fat diet

ABSTRACT: Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in obese individuals. Here, we show that macrophages accumulate within tumors of obese CRC patients and in obese CRC mice and promote accelerated tumor growth. These changes are initiated by oleic acid accumulation and subsequent tumor cell-derived acid production, and driven by signaling through GPR65, an acid-sensing receptor on CRC-associated macrophages. We demonstrate a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in obese patients with CRC or HCC also exhibit increased GPR65 expression, suggesting that the mechanism revealed here likely contributes to tumor growth in a range of obesity-associated cancers and represents a potential therapeutic target.

ORGANISM(S): Mus musculus

PROVIDER: GSE274822 | GEO | 2024/10/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA sequencing of MC38 tumor cells from control-diet- and high-fat-diet-fed C57BL/6J mice

Project description:Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in obese individuals. Here, we show that macrophages accumulate within tumors of obese CRC patients and in obese CRC mice and promote accelerated tumor growth. These changes are initiated by oleic acid accumulation and subsequent tumor cell-derived acid production, and driven by signaling through GPR65, an acid-sensing receptor on CRC-associated macrophages. We demonstrate a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in obese patients with CRC or HCC also exhibit increased GPR65 expression, suggesting that the mechanism revealed here likely contributes to tumor growth in a range of obesity-associated cancers and represents a potential therapeutic target.

2024-10-18 | GSE274825 | GEO

RNA sequencing of tumor-associated macrophages from control-diet- and high-fat-diet-fed C57BL/6J mice

2024-10-18 | GSE274824 | GEO

Tumor-Associated Macrophages Promote Colorectal Tumor Development Through Remodeling of Its Extracellular Matrix

Project description:Extracellular matrix (ECM) structural and compositional abnormalities are a hallmark of many cancers. Tumor associated macrophages (TAM) are considered pivotal players in mounting pro-tumoral functions; yet, their role in tumor-ECM remodeling remains largely ambiguous. Using an orthotopic murine model of colorectal cancer we defined two major CRC TAM subsets arising from Ly6Chi monocytes recruited in a CCR2-depedent manner. TAM-deficient CRC tumors established Ccr2-/- mice exhibited attenuated growth. Advanced imaging techniques revealed that the enhanced deposition, linearization and cross-linking of collagen fibers typical to tumor growth were absent in the Ccr2-/- tumors. Moreover, the Ccr2-/- tumors displayed altered ECM composition with 348 proteins that were differentially expressed in comparison with WT tumors, among them 46 were ECM related. Integrating transcriptomic and proteomic approaches we defined a TAM signature of ECM remodeling enzymes, structural and affiliated proteins. Specifically, were prominent proteins involved with the synthesis and assembly of collagen type I, IV and XIV. Finally, decellularized 3D ECM fragments extracted from WT tumors, but not from Ccr2-/- tumors or upstream healthy colon, enhanced tumor cell proliferation in vitro and tumor development in the native colonic environment. Collectively, our integrated biophysical-immunologic-omic approaches uncover new mechanistic insights of TAM-mediated remodeling of tumor ECM structure and composition.

2016-09-26 | PXD002094 | Pride

Proteomic analysis reveals the role of ARID1A in regulating the Wnt signaling pathway in colon cancer cells

Project description:The AT-rich interacting domain-containing protein 1A (ARID1A) is a tumor suppressor gene that has been implicated in various cancers, including colorectal cancer (CRC). The present study employed a proteomic approach to uncover the molecular mechanisms of ARID1A in CRC carcinogenesis.

2024-05-21 | PXD052413 | JPOST Repository

Crohn's disease risk variant in GPR65 alters lysosomal function

Project description:Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function. Bone marrow-derived macrophages from WT or Gpr65-/- mice were harvested for RNA analysis.

2016-06-15 | E-GEOD-69445 | biostudies-arrayexpress

Single Cell RNA Sequencing reveals heterogenous tumor associated immune cell compartment in lean vs obese mice using an MC38 tumor model

Project description:Immunotherapy is life saving for some cancer patients and while obesity can promote cancer, it may also increase immunotherapy efficacy. Mechanisms of this effect have been unclear, although obesity can promote an inflammatory state that may modify tumor infiltrating lymphocytes and tumor associated macrophage (TAM) populations in tumors. To identify mechanisms by which obesity affects anti-tumor immunity, diet-induced obese and lean C57BL/6 mice received subcutaneous murine MC38-CEA1 colon cancer tumors. Obesity increased tumor growth rate and tumor burden. Fewer immune cells were present in tumors from obese mice, and the T cells had an activated and exhausted phenotype. Macrophages in obese animals had decreased expression of iNOS2 and MHCII, supporting a weaker “M1” anti-tumor phenotype compared to lean mice. When treated with anti-PD-1 antibodies, however, obese mice had a greater absolute decrease in tumor burden than lean mice. PD-1 blockade repolarized the macrophages to an M1-phentoype in obese mice, but this did not occur in the lean mice. Mechanistically, leptin is a pro-inflammatory adipokine that is increased in obesity and may mediate enhanced anti-tumor immunity in obesity. To test the effect of leptin on tumor growth and anti-tumor immunity, lean mice were treated with leptin and tumors were observed over time. Leptin had single-agent preventative and therapeutic anti-tumor efficacy similar to PD-1 checkpoint therapy. These data demonstrate that obesity has dual effects in cancer through promotion of tumor cell initiation while also enhancing anti-tumor immunity through elevated levels of leptin that can reprogram inflammatory macrophages.

2021-10-06 | GSE179936 | GEO

CCL2/CCR2/Erk signal induced by interaction between cancer cells and macrophages contributes to hepatocellular carcinoma progression

Project description:Macrophages infiltrating into tumors are known as tumor-associated macrophages (TAMs) and play a central role in tumor progression. In immunohistochemistry, intra-tumoral CD68-positive macrophages correlated with poor prognosis and clinicopathological factors of patients with hepatocellular carcinoma (HCC). Next, we established an indirect co-culture assay between HCC cells and peripheral blood-derived macrophages. cDNA microarray analysis revealed that C-C motif chemokine ligand 2 (CCL2) was highly expressed in HCC cells co-cultured with macrophages. CCL2 bound to CCR2, known as a main receptor of CCL2, and promoted the proliferation and migration of HCC cells and macrophages. The Erk pathway as a downstream signal of the CCL2/CCR2 axis contributed to controlling these phenotypes of HCC cells and macrophages. In the ELISA using serum samples, the serum CCL2 levels of patients with HCC were significantly elevated compared with healthy volunteer donors. The survival outcomes of patients with intra-tumoral CCL2 expression Positive based on immunohistochemistry tended to be worse, without statistical significance. Consequently, the CCL2 upregulated through the interactions between HCC cells and macrophages contributed to HCC progression and the CCL2/CCR2/Erk signal might be an effective candidate for the treatment target of HCC and macrophages.

2024-12-18 | GSE274406 | GEO

Inactivation of interferon signaling promotes the establishment of an immunosuppressive microenvironment in colorectal cancers

Project description:Tumors arise and grow despite anti-cancer immune responses. These responses can be stimulated by immunotherapies such as immune checkpoint inhibitors (e.g. anti-PD1 antibodies) and chimeric antigen receptors (CAR). Efficacy of these agents in solid tumors including colorectal cancers (CRC) is limited by immunosuppressive tumor microenvironment (TME) that prevents killing of malignant cells by cytotoxic T lymphocytes (CTL). Understanding the nature of TME-generated immunosuppression is of paramount importance. Here we report that TME elicited immunosuppression via eliminating activated CTL; this elimination required TME stress-induced downregulation of the IFNAR1 chain of type I interferon (IFN) receptor and attenuation of its signaling. Downregulation of IFNAR1 was observed in human colorectal cancers (CRC) and in mouse CRC models where it was required for efficient tumor development and progression. Stabilization of IFNAR1 on CTL improved their survival and increased anti- tumor activities of CAR T cells and PD1 inhibitors thereby providing a rationale for targeting IFNAR1 degradation for immunotherapies optimization. Two genotypes of mice were examined either 9 or 21 days post injection of MC38 colon cancer cells or MC38mRFP cells, respectively. 2-3 replicate mice were analyzed on separate arrays for each condition. 6 conditions in total were analyzed.

2016-01-15 | E-GEOD-76889 | biostudies-arrayexpress

Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis

Project description:Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a pathophysiological pathway very similar to that observed in obese humans. This process initiates with non-alcoholic fatty liver disease (NAFLD), progresses to steatohepatitis and fibrosis before HCC detection, and is driven by persistent genome-wide gene deregulation that induces global liver metabolic dysfunction. Nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism are found among top deregulated pathways. Ablation of the bile acid receptor FXR dramatically increases intrahepatic bile acid levels and jet-lag-induced HCC, while loss of CAR, a well-known liver tumor promoter, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction. Thus, FXR and CAR are clock-controlled therapeutic targets for spontaneous HCC

2016-11-23 | GSE75475 | GEO