The use of patient-derived breast tissue explants to study macrophage polarization and the effects of environmental chemical exposure.

TitleThe use of patient-derived breast tissue explants to study macrophage polarization and the effects of environmental chemical exposure.
Publication TypeJournal Article
Year of Publication2020
AuthorsGregory, KJ, Morin, SM, Kubosiak, A, Ser-Dolansky, J, Schalet, BJ, D Jerry, J, Schneider, SS
JournalImmunol Cell Biol
Volume98
Issue10
Pagination883-896
Date Published2020 11
ISSN1440-1711
KeywordsBenzophenones, Breast, Cell Polarity, Endocrine Disruptors, Environmental Exposure, Female, Humans, Macrophage Activation, Macrophages, Tissue Culture Techniques
Abstract

Ex vivo mammary explant systems are an excellent model to study interactions between epithelium and stromal cell types because they contain physiologically relevant heterotypic interactions in the background of genetically diverse patients. The intact human mammary tissue, termed patient-derived explant (PDE), can be used to investigate cellular responses to a wide variety of external stimuli in situ. For this study, we examined the impact of cytokines or environmental chemicals on macrophage phenotypes. We demonstrate that we can polarize macrophages within human breast tissue PDEs toward M1 or M2 through the addition of interferon-γ (IFNγ) + lipopolysaccharide (LPS) or interleukin (IL)-4 + IL-13, respectively. Elevated expression levels of M(IFNγ + LPS) markers (HLADRA and CXCL10) or M(IL-4 + IL-13) markers (CD209 and CCL18) were observed in cytokine-treated tissues. We also examined the impact of the endocrine-disrupting chemical, benzophenone-3, on PDEs and measured significant, yet varying effects on macrophage polarization. Furthermore, a subset of the PDEs respond to IL-4 + IL-13 through downregulation of E-cadherin and upregulation of vimentin which is reminiscent of epithelial-to-mesenchymal transition (EMT) changes. Finally, we were able to show immortalized nonmalignant breast epithelial cells can exhibit EMT characteristics when exposed to growth factors secreted by M(IL-4 + IL-13) macrophages. Taken together, the PDE model system is an outstanding preclinical model to study early tissue-resident immune responses and effects on epithelial and stromal responses to stimuli found both endogenously in the breast and exogenously as a result of exposures.

DOI10.1111/imcb.12381
Alternate JournalImmunol Cell Biol
PubMed ID32713010
PubMed Central IDPMC7754397
Grant ListR01 ES015739 / ES / NIEHS NIH HHS / United States
U01 ES026140 / ES / NIEHS NIH HHS / United States