Modeling Breast Tumor Development with a Humanized Mouse Model

  • Lisa M. Arendt
Part of the Methods in Molecular Biology book series (MIMB, volume 1458)


The tumor microenvironment plays a critical role in breast cancer growth and progression to metastasis. Here, we describe a method to examine stromal–epithelial interactions during tumor formation and progression utilizing human-derived mammary epithelial cells and breast stromal cells. This method outlines the isolation of each cell type from reduction mammoplasty tissue, the culture and genetic modification of both epithelial and stromal cells using lentiviral technology, and the method of humanizing and implantation of transformed epithelial cells into the cleared mammary fat pads of immunocompromised mice. This model system may be a useful tool to dissect signaling interactions that contribute to invasive tumor behavior and therapeutic resistance.

Key words

Human-in-Mouse model Human mammary epithelial cells Breast cancer Stroma Mammary gland Stromal–epithelial interactions 



The author would like to thank Victoria Thompson for helpful discussions. This work is supported by the Susan G. Komen Foundation.


  1. 1.
    Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401CrossRefPubMedGoogle Scholar
  2. 2.
    Korkaya H, Liu S, Wicha MS (2011) Regulation of cancer stem cells by cytokine networks: attacking cancers inflammatory roots. Clin Cancer Res 17:6125–6129CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chiarugi P (2013) Cancer-associated fibroblasts and macrophages: friendly conspirators for malignancy. Oncoimmunology 2:e25563CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pickup MW, Mouw JK, Weaver VM (2014) The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 15:1243–1253CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Clark AG, Vignjevic DM (2015) Modes of cancer cell invasion and the role of the microenvironment. Curr Opin Cell Biol 36:13–22CrossRefPubMedGoogle Scholar
  7. 7.
    Klemm F, Joyce JA (2015) Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25:198–213CrossRefPubMedGoogle Scholar
  8. 8.
    Arendt LM, McCready J, Keller PJ, Baker DD, Naber SP, Seewaldt V et al (2013) Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis. Cancer Res 73:6080–6093CrossRefPubMedGoogle Scholar
  9. 9.
    Proia TA, Keller PJ, Gupta PB, Klebba I, Jones AD, Sedic M et al (2011) Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell 8:149–163CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S et al (2012) Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci U S A 108:7950–7955Google Scholar
  11. 11.
    Arendt LM, Rudnick JA, Keller PJ, Kuperwasser C (2010) Stroma in breast development and disease. Semin Cell Dev Biol 21:11–18CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Comparative Biosciences, School of Veterinary MedicineUniversity of Wisconsin-MadisonMadisonUSA

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