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A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials [microarray]

ABSTRACT: A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mouse. The line maintains stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the tumors arising in the transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found strong PD-L1 expression in the tumors and in vitro. Three distinct transplantable syngenic mouse models of mammary carcinoma were compared to identify differentially expressed genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE112723 | GEO | 2019/03/06

REPOSITORIES: GEO

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A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials [RNA-seq]

Project description:A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials.

2019-03-06 | GSE113379 | GEO

Proteomics of Mouse Syngeneic Models

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2019-12-03 | PXD011885 | Pride

RNA sequencing investigating the role of TNC in tumor progression using FVB TNC WT and TNC KO mice grafted with NT193 shC cells or NT193 shTNC cells

Project description:MMTV-NeuNT transgenic mouse model harbors an activated form of Neu (NeuNT). Mice develop stochastically multifocal mammary adenocarcinomas that metastasize to the lung (Muller et al., 1988). MMTV-NeuNT mouse model exhibits both intravascular and parenchymal metastasis which provides a good tool to comprehensively study breast cancer metastasis. In this study, we investigated the role of tenascin C (TNC) in tumor progression using the a syngeneic orthotopic grafting mouse model. NT193 cell line was isolated from MMTV-NeuNT TNC WT tumor tissue. TNC expression in these cells was turned down through shRNA strategy, giving rise to NT193 shTNC cells and their respective control NT193 shcTNC. These cells were grafted orthotopically into syngeneic FVB mice either WT or KO for TNC. In FVB WT mice, NT193 shcTNC tissue was treated with AMD3100 (plerixafor) (Sigma, A5602) at 5 mg/kg/day by peritumoral injection for 2 weeks before processing with NT193 shcTNC and NT193 shTNC tissue receiving phosphate buffered saline as a control.

2021-03-25 | E-MTAB-10135 | biostudies-arrayexpress

Comparative Analysis of MMTV-neu tumors, preneoplastic MMTV-neu mammary gland, and Wild-type controls

Project description:To identify early events of erbB2-induced mammary tumorigenesis, we compared datasets from 14 genechip experiments including MMTV-neu tumors, preneoplastic neu mammary gland (adjacent neu), and age-matched, wild-type control mammary glands Keywords = transgenic mouse Keywords = MMTV-neu Keywords = erbB2 Keywords = HER2 Keywords = mammary tumor Keywords: ordered

2005-05-03 | GSE2528 | GEO

Expression data in mouse primary mammary tumors

Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines that metastasize in syngeneic mouse hosts and we have assessed gene expression programs in the untreated primary tumors with the goal of generating information that may be useful to the identification of biomarkers that predict response to therapeutic intervention. We used microarrays to assess global gene expression programs in primary tumors from 12 metastatic mouse mammary tumor models transplanted orthotopically into syngeneic, fully immunocompetent mouse hosts. The 12 tumor models used here are based on published cell lines that had been established from either spontaneous mammary tumors or from mammary tumors arising in genetically engineered mouse models. All cell lines were previously described to be metastatic. Cells were surgically implanted in the #4 mammary fat pads of syngeneic mice and primary tumors were harvested when they reached 0.5-1.0 cm diameter and snap-frozen for later RNA extraction. 4 independent tumors were collected for each of the 12 models.

2015-05-19 | E-GEOD-69006 | biostudies-arrayexpress

Transcriptomic analysis of mammary tumor biospy from MMTV-ErbB2 transgenic mice

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2024-01-02 | GSE252001 | GEO

Expression data from C3(1)Tag mammary tumors, tumor derived cell line (M6) and normal mammary tissue (FVB)

Project description:M6 cells expression a similar genetic signature as the parent tumor, C3(1)Tag tumor. The mammary tumors, and tumor cell line, are distinct from normal mammary epithelial tissue (FVB) BRCA/p53, cmyc, h2n, p53ERneg, p53ERpos, pymt and ras samples were not reported in this paper. We used microarrays to determine whether the M6 cell line retains the SV40Tag signature (91 gene signature) that is expressed in C3(1)Tag tumors but not FVB normal mammary tissue.

2011-08-31 | E-GEOD-25488 | biostudies-arrayexpress

Genome-wide transcript analysis of ErbB2-induced tumors from different tumor-initiating cells

Project description:ErbB2-induced mouse mammary tumors can originate from different mammary epithelial cells, including both basal epithelial cells and luminal progenitors. Here we used the tumors from basal cells or luminal progenitors to compare the difference in transcripts.

2014-12-24 | GSE64487 | GEO

Expression data from C3(1)Tag mammary tumors, tumor derived cell line (M6) and normal mammary tissue (FVB)

2011-09-01 | GSE25488 | GEO

Transcriptional analysis of signal transduction-related genes in experimental models of HER-2/neu-derived epithelial and mesenchymal tumors

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2010-07-03 | E-GEOD-22663 | biostudies-arrayexpress

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