Dataset Information

The temporal progression of lung immune remodeling during breast cancer metastasis

ABSTRACT: The dynamics of immune reprogramming in the breast cancer lung metastastic niche remains incomplete. We used MULTI-seq (McGinnis, Patterson, et al., Nature Methods, 2019) to perform multiplexed single-cell RNA-sequencing analysis of cryopreserved lung immune cells isolated from PyMT mice, freshly-isolated lung immune cells isolated from PyMT mice, and cryopreserved lung immune cells isolated from 4T1 tumor-bearing mice from the onset of primary tumorigenesis through the formation of macrometastatic lesions. Cryopreserved PyMT samples were collected from 6-14 weeks of age, fresh PyMT samples were collected at 6, 10 and 13 weeks of age (with age-matched wild-type controls)

ORGANISM(S): Mus musculus

PROVIDER: GSE263963 | GEO | 2024/04/22

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Dipyridamole (DPM) is widely used to prevent strokes and vascular thrombosis. Combination therapy of DPM and antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter driven polyoma middle T oncoprotein (MMTV-PyMT) metastatic breast cancer model. We also investigated the effects of DPM on gene and miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary tumor growth kinetics and the number of lung metastases in transgenic mice treated with DPM or vehicle. Gene expression and microRNA (miRNA) expression profiles of mammary tumor tissues were then analyzed using the Affymetrix GeneChipM-BM-. or miRNA 2.0 arrays. Real-time quantitative PCR (qPCR) was used to confirm changes in gene expression. Treatment with DPM beginning at the age of four weeks delayed the onset of palpable lesions, delayed tumor progression and suppressed lung metastasis. Microarray gene expression analysis identified 253 genes differentially expressed between DPM-treated and control mammary tumors. miRNA expression analysis revealed that 53 miRNAs were altered by DPM treatment. The results indicate that DPM has chemoprevention activity against breast cancer tumorigenesis and metastasis in mice. The array analyses provide insights into potential mechanisms of DPMM-bM-^@M-^Ys chemopreventive effects, involving upregulation of several genes and miRNAs known to suppress cancer growth and/or metastasis and downregulation of genes known to promote cancer. Some of these genes have not been previously studied in breast cancer and may serve as novel molecular targets for breast cancer chemoprevention. MMTV-PyMT+ female mice were randomly divided into a DPM treatment group (n=10 mice, total of 100 glands) and a vehicle (control) group (n=7 mice, total of 70 glands). When mice were four weeks old, when hyperplasia lesions begin to develop in the FVB strain (21), DPM (10 mg/kg) or vehicle was injected IP into the peritoneum of each mouse on a 5 days on/2 days off dosing schedule for a total of 11 weeks (week one=injection one), until mice were 15 weeks of age. Each of the 10 mammary tumors per mouse was monitored until the study end point. A total six breast tumor RNA samples were used for microarray analysis, with three form mice treated with DPM and three from mice treated with vehicle.

Project description:Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipocyte-derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.) pneumoniae is a common cause of gram-negative pneumonia and sepsis. The aim of this study was to determine the effect of human ASCs on the host response during pneumosepsis in mice. For this mice were infected with K. pneumoniae via the airways to induce a gradually evolving infection in the lung cumulating in pneumosepsis. One or 6 hours (h) after infection, mice were infused intravenously with ASCs or vehicle, and euthanized after 16h or 48h respectively. The effects of freshly cultured and cryopreserved ASCs were compared, the latter formulation being more clinically relevant. Intravenously administered ASCs were visualized in lung tissue by immunostaining at 1 and 3h, but not at 15h after infusion. While early after infection ASCs did not or only modestly influence bacterial loads, they reduced bacterial burdens in lungs and distant organs at 48h. ASCs reduced the lung levels of pro-inflammatory cytokines and attenuated lung pathology, but did not influence distant organ injury. ASCs strongly modified the lung transcriptome in both uninfected mice and mice with pneumosepsis, especially affecting. Cryopreserved and cultured ASCs induced largely similar effects. These data indicate that human ASCs induce profound immune modulatory effects in the lungs, resulting in reduced bacterial burdens and lung inflammation during pneumosepsis caused by a common human pathogen, suggesting that ASCs may be an adjunctive therapeutic in this condition. Experimental groups were defined as follows: (1) plac_cryo, placebo treated and K.pneumoniae infected control mice for cryopreserved MSCs; (2) plac_cult, placebo treated and K.pneumoniae infected control mice for cultured MSCs; (3) cryo, K.pneumoniae infected mice treated with cryopreserved MSCs; (4) cult, K.pneumoniae infected mice treated with cultured MSCs; (5) n_cult, non-infected control mice for cultured MSCs; (6) n_cryo, non-infected control mice for cryopreserved MSCs; (7) n, normal mouse lung baseline. In a separate experiment, mice were treated with a selective prekallikrein (PKK) directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 hours postinfection, including genome-wide messenger RNA profiling of lungs, or mice were followed for survival Pre-processing and quality control of the scans were performed by using the oligo method (version 1.44) and probes were annotated using the platform design info for Affymetrix Clariom_S_Mouse_HT available through Bioconductor. Array data were background corrected by Robust Multi-array Average (RMA) and quantiles-normalized. Microarray quality control was performed by means of the array quality metrics method (version 3.36.0). The occurrence of non-experimental chip effects was evaluated by the surrogate variable analysis method (version 3.28.0) and corrected using the combat method.

Dataset Information

The temporal progression of lung immune remodeling during breast cancer metastasis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets