Effect of Non-small cell lung cancer (NSCLC) cell line conditioned medium (CM) on bone marrow-derived macrophages (BMDMs)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA865300 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Hyperprogressive disease (HPD) is a newly described pattern of tumor progression characterizing a percentage of cancer patients receiving an immunotherapeutic regimen based on immune checkpoint inhibitors (ICIs), such as anti-PD1/PDL1 antibodies. Patients experiencing HPD are characterized by an unpredictable acceleration of tumor growth and a deterioration of the clinical conditions, rapidly leading to death. We have previously reported that macrophages play a pivotal role in contributing to HPD development. By analyzing non-small cell lung cancer (NSCLC) patient tumor samples, we observed that the tumor microenvironment (TME) of HPD-patients was infiltrated by particular clusters of macrophages. These macrophages are present before the initiation of ICI therapy and, therefore, we hypothesized that certain tumor cells may induce the acquisition of an “HPD-related” phenotype in macrophages that upon interaction with anti-PD1 antibody can unleash HPD. Since one of the strategies exploited by cancer cells to educate macrophage is to secrete molecules with immunomodulatory activity in the TME, bone marrow-derived macrophages (BMDMs) were exposed for 24 hours to the conditioned medium (CMs) obtained from five different NSCLC cell lines. We found that macrophages exposed to the CMs obtained from NCI-H460 and PC9 cell lines, reported to undergo a HPD-like growth in immunocompromised mice after anti-PD1 antibody treatment, have a gene expression profile completely different compared to the other experimental groups. Our findings suggest that soluble factors released by tumor cells can reprogram macrophages towards a phenotype potentially able to trigger HPD after interaction with anti-PD1 antibody.
2023-01-11 | GSE210340 | GEO
Project description:A functional vascular system is a prerequisite for bone repair as disturbed angiogenesis often causes non-union. Paracrine factors released from human bone marrow mesenchymal stromal cells (BMSCs) have angiogenic effects on endothelial cells. However, whether these paracrine factors participate in blood flow dynamics within bone capillaries remains poorly understood. Here, we used two different microfluidic designs to investigate critical steps during angiogenesis and found pronounced effects of endothelial cell proliferation as well as chemotactic and mechanotactic migration induced by BMSC conditioned medium (CM). The application of BMSC-CM in dynamic cultures demonstrates that bioactive factors in combination with fluidic flow-induced biomechanical signals significantly enhanced endothelial cell migration. Transcriptional analyses of endothelial cells demonstrate the induction of a unique gene expression profile related to tricarboxylic acid cycle and energy metabolism by the combination of BMSC-CM factors and shear stress, which opens an interesting new avenue to explore during fracture healing. Our results stress the importance of in vivo - like microenvironments simultaneously including biochemical, biomechanical and oxygen levels when investigating key events during vessel repair.
2023-01-01 | GSE208335 | GEO
Project description:Bone metastases is a common severe complication for breast cancer. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced breast cancer cell extravasation across endothelial monolayers. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. Therefore, we used RNA sequencing to show that CM from endothelial cells conditioned in CM from flow-stimulated osteocytes significantly altered gene expression in bone-metastatic breast cancer cells. This This provides insights into the capability of bone-loading activity in preventing bone metastases.
2018-11-13 | E-MTAB-7176 | biostudies-arrayexpress
Project description:The effect of human gingival fibroblast-conditioned medium (HGF-CM) on pulp regeneration
| PRJNA832119 | ENA
Project description:HGF-CM increases the proliferation and migration ability of DPSC (Dental pulp stem cells) in a dosage dependent manner, and facilitates the mineralization of DPSC by upregulating odotogenic genes. Although lack of in vitro evidence, DPSC and hGF-CM could be a promising combination for pulp regeneration in the future.
2022-10-29 | GSE201524 | GEO
Project description:Purpose: The goals of this study are to compare transcriptomic profiling (RNA-seq) of BMDMs activated by CM generated from CO-Fibs and PH-Fibs and to evaluate the mechanisms how healthy and pulmonary hypertensive adventitial microenvironment maintain or activate macrophage phenotypes. Methods: Mouse BMDMs were treated with media conditioned by CO-Fibs (CO-CM) or PH-Fibs (PH-CM) or left untreated (UNX). Each CM was pooled from 5 different fibroblast populations. Total RNA was purified using NucleoSpin RNA Isolation kit (Machery-Nagel, www.mn-net.com) according to the manufacturer’s instructions. RNA quantity and quality were evaluated using NanoDrop and Bioanalyzer. For Transcriptomics analysis, RNA-Seq library preparation and sequencing were conducted using a NuGen universal plus mRNA-Seq kit. Sequencing was performed on Illumina NovaSEQ6000 system, using the paired-read 2x150 cycle option. RNA-Seq reads were generated using Illumina NovaSEQ6000 analysis pipeline. The read quality of all the samples were checked using FastQC v0.11.5. Adapter trimming, quality control, and base correction were performed by AfterQC (Chen et al., 2017). The sequencing reads in the FASTQ files of all the samples were aligned to the Mus musculus reference genome (Mus_musculus. GRCm38v91) with Spliced Transcripts Alignment to a Reference (STAR) version 2.6.0c. We next applied featureCounts v1.6.2 to assign reads to genes using mouse transcript annotations as a guide. EdgeR in R was used for data normalization and differential expression analysis of RNA-Seq expression profiles with biological replication. The Benjamini-Hochberg procedure was used to control the false discovery rate (FDR), and a cut-off criterion of FDR ≤ 0.05 was applied to identify differentially expressed genes. Individual gene expression was calculated as ‘reads per kilobase per million mapped reads’ (RPKM). Results: Using a standard data analysis workflow (STAR-featureounts-edgeR), our results showed that both CO-CM and PH-CM had significant, yet clearly different, effects on gene expression in BMDMs. Principal component analysis (PCA) of all 12,191 genes showed overall separation of CO-CM and PH-CM treated BMDMs from untreated BMDMs. To obtain insight into the underlying mechanisms through which microenvironments regulate macrophage phenotype and function in control and diseased conditions, we analyzed genes uniquely regulated by CO-CM or PH-CM vs. naïve BMDM using Ingenuity Pathway Analysis (IPA). Canonical signaling pathways identified by IPA demonstrated that CO-CM significantly inhibited inflammatory pathways (role of pattern recognition receptors), immune responses (PD-1, PD-L1 cancer immunotherapy pathway, Tec Kinase signal, and T cell exhaustion signal), lipid (3-phosphoinositide) metabolism and glycolysis suggesting a metabolically quiescent and anti-inflammatory phenotype. In contrast, when the microenvironment was dictated by disease (i.e., PH-CM), macrophages exhibited distinct upregulated canonical pathways, particularly those related to inflammation (iNOS, Toll-like receptor, NF-kB, TNFR, etc.) and activated immune responses (Th1 pathway, T cell exhaustion signaling pathway, dendritic cell maturation). Pathways involved in metabolism were also notably altered with increased NO and ROS production, and decreased oxidative phosphorylation indicating altered mitochondrial function. Conclusions: Results from our study provide the basis for a more systematic mechanistic understanding of the cross-talk between adventitial fibroblasts and macrophages in health and disease by revealing a comprehensive view of the macrophage transcriptomic and metabolomic landscape.
2021-03-16 | GSE165500 | GEO
Project description:We have employed whole genome microarray to identify changes in gene expression in human MSCs exposed to tumor conditioned medium Human MSC line (hMSC-TERT) was exposed to tumor conditioned medium (CM) from FaDu hypo pharyngeal cancer cell line for 7 day. Subsequently, RNA was extracted using Roche MagNA Pure automated nucleic acid purification system. Control RNA was collected from the same batch of MSCs exposed to normal medium. Extracted RNA was labeled and then hybridized to the one-color Agilent Human GE 4x44K v2 Microarray chip.
2013-09-11 | E-GEOD-50722 | biostudies-arrayexpress
Project description:The disturbance of adipose tissue in obesity highly correlates with cancer progression. To investigate the impacts of obesity on triple-negative breast cancer (TNBC), we performed an in vitro system culturing TNBC cells with human white adipocytes-conditioned medium (hAd-CM). The gene expression profiling between each condition was then assessed by RNA-seq.
2023-01-25 | GSE209894 | GEO
Project description:Malignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions. Huvec cells were grown in melanoma conditioned medium or DMEM 10% FCS for 12 h under hypoxic or normoxic conditions. In order to identify the transcripts modulated by melanoma CM, samples treated with MCM were compared to those grown in DMEM alone.
2013-09-30 | E-GEOD-33115 | biostudies-arrayexpress
Project description:We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. Myoblasts were incubated with control or pancreatic cancer CM for 14 and 24 hours. Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic. Keywords: Mice myoblasts, pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3), cDNA microarrays
2005-10-05 | GSE3409 | GEO