Comparative profiling of metastatic 4T1- versus non-metastatic Py230-based mammary tumors in an intraductal model for triple-negative breast cancer.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA588756 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10428200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10428200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10428201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10428201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10428202_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 144 |
Similar Datasets
Project description:Purpose: Compare the tumor outgrowth and immunology of an immunocompetent 4T1- and Py230-based intraductal model for triple-negative breast cancer (TNBC). Methods: BALB/c-derived 4T1 and C57BL/6-derived Py230 mammary tumor cells were side-by-side intraductally inoculated in lactating and syngeneic mice, 4T1 and Py230 primary tumors were subsequently resected at 1, 3 and 6 weeks (w) post-inoculation (p.i.), and RNA was isolated from the 4T1 and Py230 primary tumors using in house developed protocols. Results: The differentially expressed genes in the 4T1 versus Py230 primary tumor datasets at the 3 different time points were categorized into 28 hallmark gene sets using GSEA. Nine hallmarks could be related to tumor immunology and collectively showed a decreased difference in expression over time, although every immunology-related gene set remained most expressed in 4T1 primary tumors across all time points. Seven hallmarks could be related to cellular mitosis and tumor progression and were significantly upregulated at 1 w p.i. in 4T1 primary tumors, whereas at 3 w p.i. they became significantly upregulated in Py230 primary tumors, indicative for enhanced Py230 tumor proliferation. The hallmark epithelial-mesenchymal transition was significantly upregulated at 3 w p.i. in 4T1 compared to Py230 primary tumors, indicative for metastatic progression. Gene sets involved in adipose/stromal processes within the mammary gland were downregulated or weakly expressed at 1 w p.i., but became upregulated at 3 w p.i. in 4T1 compared to Py230 primary tumors, indicating that at the time 4T1 tumor cells were less proliferative compared to Py230 tumor cells, the surrounding stroma and fat tissue were more active in the 4T1- compared to the Py230-based intraductal model. The hallmark androgen response also showed a significantly upregulated expression in Py230 tumors at 3 and 6 w p.i., indicating that androgen signaling is important in invasive Py230 tumors. Conclusion: Our findings highlight an innovative 4T1- and Py230-based intraductal mouse model for TNBC with a different tumor outgrowth and associated tumor microenvironment. These differential models may broadly represent the clinically observed TNBC diversity and together provide a powerful tool to evaluate therapeutics.
2019-11-20 | GSE140192 | GEO
Project description:The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma (IC) in breast cancer can be faithfully reproduced by the intraductal mouse model. Envisaging to use this model for therapeutic testing, we aimed to in-depth characterize the tumor immunity associated with the differential progression of two types of intraductal tumors. More specifically, we focused on triple-negative breast cancer (TNBC) and intraductally inoculated luciferase-expressing metastatic 4T1 and locally invasive Py230 cells in lactating mammary glands of syngeneic BALB/c and C57BL/6 female mice, respectively. Although the aggressive 4T1 cells rapidly formed solid tumors, Py230 tumors eventually grew to a similar size through enhanced proliferation. Yet, ductal tumor cell breakthrough and metastasis occurred earlier in the 4T1- compared to the Py230-based intraductal model and was associated with high expression of matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), chitinase 3-like 1 (CHI3L1) and lipocalin 2 (LCN2) as well as an increased influx of immune cells (mainly macrophages, neutrophils and T-cells). Moreover, activated cytotoxic T-cells, B-cells and programmed death-1 (PD-1)-positive cells were more prominent in the 4T1-based intraductal model in line with enhanced pro-inflammatory cytokine and gene expression profiles. Py230-based tumors showed a more immunosuppressed anti-inflammatory profile with a high amount of regulatory T-cells, which may account for the decreased T-cell activation but increased proliferation compared to the 4T1-based tumors. Taken together, our results highlight the differential immunological aspects of aggressive metastatic and non-aggressive intraductal progression of 4T1- vs. Py230-based tumors, providing a base for future studies to explore therapy using these intraductal TNBC models.
| S-EPMC6927949 | biostudies-literature
Project description:We used 4T1 murine breast cancer cells to establish a syngeneic tumor model and found that liver metastatic cells exhibited serveral biological and molecular characteristic that are distinct from parental 4T1 cells. We used microarrays to analyze 4T1-3R_L cells exhibited several CSC related genes compared to 4T1 cells.
2022-07-29 | GSE181102 | GEO
Project description:Using bulk RNA-seq, the transcriptional profile of two cell lines with high or low metastatic properties derived from single clones of the murine 4T1 cell line treated or untreated with iron chelator DFX was analyzed in order to determine the mechanism underlying the inhibition preference of DFX for highly metastatic 4T1 cells.
2022-11-16 | GSE218133 | GEO
Project description:This laboratory's focus is on the immune response to carbohydrate antigens, with an emphasis on modalities to analyze and to increase the immune response. We are also interested in carbohydrate drug targeting. The hypothesis is that these 2 variants have different cell surface carbohydrate expression, which results in different adhesion patterns, which ultimately results in different metastasis patterns. Evidence for expression differences and loss of the variants ability to metastasize to the lung could have clinical implications in the prevention of metastasis to different organs. The 4T1 mouse metastatic breast cancer cell line is known to change with passages in culture. Our data has shown changes cause the cells to metastasize to the intestine rather than to the lung. Four classes of RNA were analyzed: one each from 4T1 metastatic cell line variant #1, 4T1 variant #2, non-metastatic cell lines 4T07, and non-metastatic cell line 67NR. Classes were prepared in triplicate for a total of 12 samples. All samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.
2011-02-17 | E-GEOD-27354 | biostudies-arrayexpress
Project description:Expression data from 4T1 parental breast cancer cell line and 4T1-3R liver metastatic cells (4T1-3R_L).
| PRJNA750718 | ENA
Project description:MCT-1 (malignant T cell amplified sequence) is an oncoprotein encoded by Mcts1 gene that regulates translation re-initiation, ribosomal recycling, and tumorigenicity. We have characterized the metastasis cascade, immune evasion,and inflammatory responses which are suppressed by silencing of MCT-1 (shMCT-1) through transcriptional profiling of the 4T1 metastatic TNBC cell line. shMCT-1-altered gene lists are related to the IFNα-response, IFNγ-response, IL-6/JAK/STAT pathway, inflammatory response. shMCT-1 also suppresses expression of upstream regulators of PD-L1 and epidermal growth factor receptor (EGFR) ligands as compared to scramble cells.
2022-06-25 | GSE206910 | GEO
Project description:We aimed at characterizing the response to reduced cPLA2α activity in metastatic versus non-metastatic cells. We employed an isogenic murine cell line pair displaying metastatic (4T1) and non-metastatic (67NR) phenotype to investigate the role of cPLA2α on migration. Further, we elucidate the effect of reduced cPLA2α activity on global gene expression in the metastatic cell line We found that cPLA2α inhibition may inhibit metastasis through an anti-migratory effect, possibly involving Toll-like receptor signaling and type I interferons
2019-09-26 | GSE138026 | GEO
Project description:Metabolic rewiring is essential for breast tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. Transcriptional and metabolomic analysis have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic profile characterized by increased HIF-1α activity and dependence on glycolysis. Stable isotope tracing analysis (SITA) performed in vivo confirmed that the glycolytic nature of liver-metastatic breast cancer cells is retained when these cells are grown as primary tumors or as liver metastases. However, our data also reveal that unique metabolic adaptations are specifically induced by the liver microenvironment. Indeed, liver metastases display elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to primary tumors. Moreover, breast cancer liver metastases rely strongly on glucose and glutamine-derived carbons to support de novo GSH synthesis. Glutathione is a tripeptide that acts as a major scavenger for reactive oxygen species (ROS). Liver metastases display reduced levels of 8-Oxo-2'-deoxyguanosine, confirming their increased capacity to buffer ROS. We demonstrated the dependence of liver metastases formation on these distinct metabolic adaptations by depleting glutamate-cysteine ligase (Gcl), the rate-limiting enzyme in glutathione biosynthesis. Gcl depletion, and decreased GSH levels, strongly reduced the capacity of liver-metastatic cells to form distant metastasis within the liver. We performed gene expression analysis of liver metastasis and primary tumors from liver-metastatic breast cancer cells derived from 4T1 cells. 4T1-2776 (76) and 4T1-2792 (92) cells were injected in the mammary fat pads of BALB/c and grown as primary tumors or were grown as liver metastasis after splenic injection. Tissues were harvested from primary tumors and liver metastasis and submitted to laser-capture microdissection (LCM). For liver metastasis, tumour tissue was harvested at 10 days, 2 weeks and 3 weeks after splenic injection. For each time point, tissue was isolated from the tumor centre (core), a peripheral area of the tumor (margin), a region of the liver proximal to the tumor (adjacent) and a region of the liver far from the tumor (distant). For primary tumors from 4T1-2776 cells (1034, 1036, 1043) and 4T1-2792 (MFP2L, MFP3L, MFP5L) tissue was collected from the tumor core and margin, at the experimental endpoint.
2023-07-25 | GSE238214 | GEO
Project description:Recently, cancer immunotherapy has been paid much attention because of its improved efficacy and low frequency of adverse effects. A mouse breast cancer cell line, 4T1, has been known as poorly immunogeneic and highly metastatic cell line. In this study, we have identified a sub cell line of 4T1, designated as 4T1-Sapporo (4T1-S), which could induce a strong immune response against the same line. When 4T1-S was subcutaneously injected, striking enlargement of draining lymph nodes and increase of activated T cells were observed. The strong immune responses could not be observed when 4T1-S was injected to nude mice, indicating that this phenomenon is mediated by T cell response. Identification of 4T1-S characteristics may help to improve immunotherapy against breast cancer. 4T1-A1, 4T1-A2, 4T1-S1, 4T1-S2
2015-11-01 | E-GEOD-71926 | biostudies-arrayexpress