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A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials

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Abstract

In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDLUCD”. The cell line 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. NDLUCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDLUCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDLUCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1fvb2 and FVB/NTg(MMTV-PyVTY315F/Y322F) derived DB-7fvb2 cell lines. The NDLUCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.

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Data Availability

The microarray and RNASeq datasets generated during the current study are available in the NCBI Gene Expression Omnibus repository, under accession number GSE113380. The scanned slides of immunohistochemical stainings are available from the corresponding author on reasonable request. All further data are published in the manuscript.

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Funding

The UC Davis Comprehensive Cancer Center Genomics Shared Resource is supported by Cancer Center Support Grant (P30CA093373) from the National Cancer Institute. The study was supported by U01 CA196406 from the National Cancer Institute’s Molecular and Cellular Characterization of Screen Detected Lesions Consortium and U01 CA141582 from the National Cancer Institute’s Mouse Models of Human Cancers Consortium.

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Authors and Affiliations

  1. Center for Comparative Medicine, University of California at Davis, Davis, CA, USA

    Zsófia Pénzváltó, Jane Qian Chen & Alexander D. Borowsky

  2. Department of Biochemistry and Molecular Medicine, School of Medicine, University of California at Davis, Sacramento, CA, USA

    Clifford G. Tepper, Maxine Umeh-Garcia & Colleen Sweeney

  3. Department of Pathology and Laboratory Medicine, School of Medicine, University of California at Davis, Sacramento, CA, USA

    Ryan R. Davis & Alexander D. Borowsky

  4. Department of Biomedical Engineering, University of California at Davis, Sacramento, CA, USA

    Matthew T. Silvestrini

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  1. Zsófia Pénzváltó
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  2. Jane Qian Chen
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  6. Maxine Umeh-Garcia
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  7. Colleen Sweeney
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Correspondence to Alexander D. Borowsky.

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Supplementary material 1

The full list of the significant differentially expressed probes between Met-1fvb2, NDLUCD and SSM2 tumors. (XLSX 113 kb)

Supplementary material 2

Significantly enriched gene ontology categories and KEGG pathways of the genes which were significantly differentially expressed between NDLUCD, SSM2 and Met-1fvb2 tumors. (XLSX 85 kb)

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Pénzváltó, Z., Chen, J.Q., Tepper, C.G. et al. A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. J Mammary Gland Biol Neoplasia 24, 149–162 (2019). https://doi.org/10.1007/s10911-019-09425-3

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  • DOI: https://doi.org/10.1007/s10911-019-09425-3

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