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01.12.2014 | Preclinical Study | Ausgabe 3/2014

Breast Cancer Research and Treatment 3/2014

Natural history of tumor growth and immune modulation in common spontaneous murine mammary tumor models

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2014
Autoren:
Ekram Gad, Lauren Rastetter, Meredith Slota, Marlese Koehnlein, Piper M. Treuting, Yushe Dang, Sasha Stanton, Mary L. Disis
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10549-014-3199-9) contains supplementary material, which is available to authorized users.
Ekram Gad and Lauren Rastetter have contributed equally to this work.

Abstract

Recent studies in patients with breast cancer suggest the immune microenvironment influences response to therapy. We aimed to evaluate the relationship between growth rates of tumors in common spontaneous mammary tumor models and immune biomarkers evaluated in the tumor and blood. TgMMTV-neu and C3(1)-Tag transgenic mice were followed longitudinally from birth, and MPA–DMBA-treated mice from the time of carcinogen administration, for the development of mammary tumors. Tumor-infiltrating CD4+ and CD8+ T-cells, FOXP3+ T-regulatory cells, and myeloid-derived suppressor cells were assessed by flow cytometry. Serum cytokines were evaluated in subsets of mice. Fine needle aspirates of tumors were collected and RNA was isolated to determine levels of immune and proliferation markers. Age of tumor onset and kinetics of tumor growth were significantly different among the models. Mammary tumors from TgMMTV-neu contained a lower CD8/CD4 ratio than that of other models (p < 0.05). MPA–DMBA-induced tumors contained a higher percentage of FOXP3+ CD4+ T-cells (p < 0.01) and MDSC (p < 0.001) compared with the other models. Individuals with significantly slower tumor growth demonstrated higher levels of Type I serum cytokines prior to the development of lesions compared to those with rapid tumor growth. Moreover, the tumors of animals with more rapid tumor growth demonstrated a significant increase in the expression of genes associated with Type II immunity than those with slower-progressing tumors. These data provide a foundation for the development of in vivo models to explore the relationship between endogenous immunity and response to standard therapies for breast cancer.

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Zusatzmaterial
Supplementary material 1 (DOCX 1061 kb)
10549_2014_3199_MOESM1_ESM.docx
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