The mammary gland is composed of a glandular ductal network. These ducts are lined by a protective layer of epithelial cells, and also contain myoepithelial cells that aid in contraction. The terminal duct-lobular unit, which makes up the terminal collecting duct within the breast is thought to be where breast cancer initiates. Breast cancer is one of the most deadly cancers worldwide and is driven by activation of oncogenes (HER2) and inhibition of tumor suppressor genes (BRCA1, BRCA2, p53). Laboratory models to study breast cancer include in vitro models using human breast cancer cells, as well as in vivo models, including genetic models or injection of breast cancer cells into the mammary fat pad.
Here at Lifeline®, we offer human male and female primary mammary epithelial cells to study normal mammary gland homeostasis, as well as disease. Lifeline® mammary epithelial cells are optimized for growth in MammaryLife™ Medium, which importantly, is phenol red-free. Since mammary epithelial cells respond to estrogen, it is important that our culture media is free of phenol red, which weakly activates the estrogen receptor, and may cause off-target signaling effects.
Additionally, Lifeline® mammary epithelial cells are a mixed population that stain positive for multiple epithelial subpopulations, including Cytokeratin14-positive myoepithelial cells, Cytokeratin 8/18-positive luminal cells, and a Cytokeratin 19-positive luminal subpopulation.
Improving Breast Cancer Screening Using Lifeline® Mammary Epithelial Cells
Breast cancer is one of the most deadly cancers in women, and like all cancers, screening and detection of early stage disease is critical for good patient outcomes. In a study from 2015, Ueo and colleagues reported the successful application of a new cancer screening method that takes advantage of the enzyme γ-glutamyltransferase (GGT), which is expressed in breast cancer cells, but not in normal cells.
The researchers took advantage of this cancer-specific expression and developed a fluorescent probe that is activated in the presence of GGT; therefore, tumor cells that express GGT should release a green fluorescent signal that is readily detectable. In this study, the authors set out to test this probe in the setting of breast-conserving surgery to improve detection of the tumor margin and prevent tumor recurrence.
The authors confirmed that multiple breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3, and CRL-1500) express GGT and activate the probe. Additionally, the authors utilized Lifeline® human mammary epithelial cells that were immortalized and cultured in MammaryLife® Basal Medium. Upon immortalization, these mammary epithelial cells expressed GGT, unlike normal mammary tissue.
To demonstrate the utility of this detection method in patients, the authors administered the probe to freshly isolated human breast samples and found that the samples that activated the probe and displayed a fluorescent signal contained abnormal lesions. Importantly, GGT was expressed in ~83% of breast tumor lesions, but was not expressed in normal breast tissue, supporting the use of this method for detecting abnormal tissue. Together, the results of this study demonstrate that this fluorescent screening method has promise for detection of breast cancer lesions, particularly during surgery.
A second reference for Lifeline® mammary epithelial cells in the literature was discussed in a previous blog. In this study, Wang et al. investigated how radiation resistance in breast cancer develops, and tested the use of disulfiram and copper as a treatment to prevent the process. A more detailed summary of this reference can be found here: Optimal Systems for Breast Cancer Research.
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