Optimal Model Systems for Breast Cancer Research

According to the National Breast Cancer Foundation, 1 in 8 women will get breast cancer in their lifetime. This translates to approximately 220,000 diagnoses and more than 40,000 deaths per year in the US. Breast cancer is the most common cancer diagnosis and the second leading cause of death in women. This devastating disease also affects men although much more rarely: approximately 2,150 men are diagnosed and 410 die of breast cancer in the US each year.

With the help of doctors and scientists, the number of deaths due to breast cancer has steadily declined in the past few decades. Early detection by routine breast exams and genetic screening of at-risk individuals combined with aggressive and effective treatment methods (breast removal surgery, chemotherapy, radiation, drug treatments) are responsible for this decline.

Better Treatment Options Still Needed

Because of the heterogeneity of breast cancer (numerous subtypes exist that affect different breast cell types or tissue structures), scientists are striving to develop better treatment options including combination therapies, targeted therapies and cancer vaccines.

The development of novel breast cancer treatments requires the use of appropriate animal and human models. Tumor biopsies from breast cancer patients provide extremely useful information into the pathology and genetics of different breast cancer subtypes. Transgenic mice that overexpress human oncogenes like c-myc or ErbB-2 and knockout mice that are deficient in human tumor suppressor genes like p53 have also proven to be useful.

Some of the more powerful models however are normal human breast cells and breast cancer cells, which allow the study of mammary cell biology and breast cancer development both in vitro and in vivo (for example human cancer cells can be xenografted into mice). Breast cancer cells also can be used in high throughput drug screening platforms to identify new cancer therapeutics.

Human breast cancer lines are typically derived from primary tumors. Normal breast cells are derived from healthy mammary tissue and are a mix of different mammary epithelial cell types. The female breast is made up of fatty tissue, lymph nodes, ducts, lobes, and lobules (Figure 1). The lobes and ducts within the breast are lined with an epithelial cell bilayer consisting of luminal epithelial cells and myoepithelial cells. The anatomy of the male breast is similar except that it lacks the specialized lobules that are responsible for milk production. These mammary epithelial cells are the most common source for breast cancer development. Thus, studying breast cancer cells and healthy mammary epithelial cells in combination will provide an optimal model system for breast cancer research.

Lifeline® Normal Human Mammary Epithelial Cells from Male and Female Tissue

Lifeline Cell Technology® offers normal human mammary epithelial cells (HMECs) derived from both female and male mammary tissue. HMECs can be used for modeling breast cancer development, basic biology research, drug development, and carcinogen screening. HMECs are cryopreserved as tertiary cells and have a guaranteed performance of at least 15 population doublings in culture. Both female and male HMECs are a mixed culture of epithelial cells that express different mammary epithelial subtype markers including Cytokeratin 14 (myoepithelial), Cytokeratin 8/18 (luminal), and Cytokeratin 19 (luminal subpopulation).

Human Mammary Epithelial Cells achieve their optimal performance when cultured in Lifeline® MammaryLife medium supplemented with MammaryLife LifeFactors. This medium comes free of serum, phenol red, and antimicrobials in order to have minimal effects on your experimental results. Additionally, HMECs can be grown in 3D cultures, which provide a more physiologically relevant model of breast cancer cell growth and behavior. Many studies have shown that gene expression profiles, cell growth, and morphology of 3D cultured cancer cell lines are more representative of tumor cell invasiveness and tissue origin.

Human Mammary Epithelial Cells in Action

 The following study illustrates what you can do with our HMECs:

• Wang et al. recently used Lifeline® normal HMECs to understand and tackle the problem of radiation-resistant breast cancer cells. Radiation therapy (RT) is often used as a post-surgery treatment for breast cancer. However, the presence of RT-resistant breast cancer stem cells can cause tumor recurrence, and RT itself can cause differentiated breast cells to revert back to a breast cancer stem cells (BCSCs). This study found that irradiated (IR) mice with syngeneic mammary tumors had increased spontaneous metastases in the lungs due to IR-induced BCSC reprogramming. Treatment with the inhibitor disulfiram (DSF) and Copper (Cu2+) was able to prevent the BCSC reprogramming of differentiated breast cells by blocking NF-kB activation. Irradiated mice receiving DSF/Cu treatment had significantly reduced primary tumor growth and spontaneous lung metastases. Furthermore, DSF/Cu or DSF/Cu with irradiation did not exhibit toxicity in Lifeline’s normal HMECsin vitro. Thus DSF/Cu in combination with RT has the potential to be an effective and non-toxic treatment for breast cancer.

Are you working on breast cancer research?

Try out our male and female HMECs in your future experiments and let us know how they work for you.