A novel and cost-effective ex vivo orthotopic model for the study of human breast cancer in mouse mammary gland organ culture

Abstract

Mouse mammary organ culture (MMOC) is used to evaluate the efficacy of chemopreventive agents against the development of carcinogen-induced preneoplastic lesions and is highly correlative to in vivo carcinogenesis models. Here, we developed a new ex vivo MMOC model, by introducing human breast cancer cells into the mouse mammary gland. This novel model, termed human breast cancer in MMOC (BCa-MMOC), mimics in vivo orthotopic breast cancer mouse models. To develop this model, estradiol-and progesterone-sensitized female mice were injected with letrozole-sensitive and-resistant T47D breast cancer cells in the mammary glands and then euthanized. The glands were cultured in vitro with hormonesupplemented media. On day 25, the glands were fixed and processed by histopathology and immunohistochemistry to evaluate for the presence of T47D cells, growth pattern, cancer markers and estradiol responsiveness. Histopathological analyses demonstrated an identical pattern of growth between the breast cancer cells injected ex vivo and in vivo. Interestingly, clusters of cancer cells in the mammary gland stroma appeared similar to those observed in human breast tumors. The injected T47D cells survived and proliferated for 15 days maintaining expression of estrogen receptor alpha (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), and aromatase. The aromataseoverexpressing T47D grown in the BCa-MMOC sufficiently metabolized estrogen, resulting in enhanced cell proliferation, induction of estrogen target genes (i.e. ER and PR-B), and showed typical changes to estrogenic milieu. In summary, here we show a novel, inexpensive ex vivo model, to potentially study the effects of therapeutic agents on cancer cells grown in an orthotopic micromilieu. This article has an associated First Person interview with the first author of the paper.

Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis

“…Unlike the LTLT-Ca cells, the T47DaromLR cells retained the ER and remain sensitive to the growth inhibitory effects of fulvestrant. In our previously published study, using the T47D-derived cell lines, immunofluorescence staining was performed to compare ER localization [ 22 ]. When compared to the T47Dcon cells, both the T47Darom and T47DaromLR cells, which express increased aromatase, exhibited increased nuclear localization of the ER in the absence of hormone treatment.…”

Improved Fuzzy C-Means Clustering Algorithm-Based Dynamic Contrast-Enhanced Magnetic Resonance Imaging Features in the Diagnosis of Invasive Breast Carcinoma before and after Menopause

“…It is a malignant tumor with various morphology, molecular characteristics, clinical courses of disease, and therapeutic response [ 14 ]. The prognosis of patients with breast carcinoma is affected by multiple factors, including not only gender, age, lifestyle, and treatment plan but also tumor morphology, pathological levels, lymph node status, immunohistochemical indexes, and gene expression [ 15 , 16 ].…”

Theragnostic nanomotors: Successes and upcoming challenges

“…These systems offer precise control over various experimental parameters while accounting for the influence of the tissue microenvironment, cell-cell connections, and cell-matrix interactions. (Ahonen et al, 2017;Begum et al, 2020;A. Gupta et al, 2020;Sakagami, 2006;Takahashi et al, 2020;van de Merbel et al, 2018).…”