to isolate a single mouse breast cell based on its specific surface proteins, visualize it under a microscope, and demonstrate its capacity to regenerate a complete functional mammary gland when transplanted into a cleared fat pad of a recipient mouse. Clonal outgrowths obtained from the recipient mouse were further transplanted into another recipient and were once again shown to regenerate a complete functional gland, which meant that the outgrowth must been generated from the self-renewing mammary stem cell. These cells were found to be localized to the basal cell population in the gland where the myoepithelial cells are present. MaSCs are difficult to identify with precision because they represent a small percentage of the basal cells, and markers to identify them are still being researched. Advances in cell dissection, isolation, and sorting techniques will also enable more accurate separation of MaSCs from other cell types in the basal cell population. Identification of lineage-restricted luminal and myoepithelial progenitors has had significantly more success, with a specific population of progenitors having been identified based both on cell surface markers and the presence or absence of receptors for the hormones estrogen and progesterone. After the identification of MaSCs in the mouse in 2006, distinct luminal progenitor cell populations were also identified. Following this, MaSCs and luminal progenitors have also been identified in humans by various research groups.
More recently, a study published in 2013 has identified a small population of cells in the human breast that exhibit significant multilineage differentiation capacity. When these cells were isolated from a larger population of mammary epithelial cells and cultured in the lab, they exhibited a capacity to differentiate into both luminal and myoepithelial cells. They were also shown to be capable of forming alveolar structures in culture. When these human cells were transplanted on to the cleared fat pads of immunodeficient mice, they also formed glandular and ductal outgrowths, showing a distinct capacity to repopulate the breast with all three cell types present. These cells were termed endogenous plastic somatic (ePS) cells. Further study demonstrated that when ePS cells were isolated from this epithelial population each of these cells were capable of differentiating into all three germ layers, indicating the presence of pluripotency characteristics. However, these cells were shown to be distinct from embryonic stem cells, induced pluripotent stem cells, or multipotent mesenchymal stem cells in that they cannot proliferate indefinitely.
Potential Role of MaSCs in Breast Cancer
One of the more direct implications of the presence of stem cells in the breast is their potential role in breast cancer. Breast cancer is one of the most common cancers among women, and significant basic and clinical research efforts have focused on understanding the biology of breast cancer to develop effective therapeutic strategies. The self-renewing nature of stem cells presents an ideal source for the origin of highly proliferative malignant tumors. With increasing knowledge of the role that stem cells may play in cancer (cancer stem cells) and the presence of stem and progenitor cells in the breast, there has been several research efforts focused on determining the presence or role of potential breast cancer stem cells. Breast cancer stem cells were first identified in 2003 based on the presence or absence of specific molecules on the cell surface. A combination of the expression of the molecule CD44 and the lack of or low expression of the molecule CD24 was used to identify breast cancer stem cells. In addition, another marker for these cells is the expression of the enzyme aldehyde dehydrogenase (ALDH). Together the presence of CD44 and ALDH expression and low or absent expression of CD24 represents the most widely used identifiers for isolating breast cancer stem cells. When these cells were isolated and transplanted into immunodeficient mice, they generated tumors. However, these proteins are not the most accurate markers, and current research efforts are being directed at discovering other markers.
Arvind Suresh
Independent Scholar
See Also: Breast: Cell Types Composing the Tissue; Breast: Current Research on Isolation or Production of Therapeutic Cells; Breast: Development and Regeneration Potential.
Further Readings
Fu, Naiyang, Geoffrey J. Lindeman, and Jane E. Visvader. “The Mammary Stem Cell Hierarchy.” Current Topics in Developmental Biology, v.107 (2014).
Guo, Wenjun. “Concise Review: Breast Cancer Stem Cells: Regulatory Networks, Stem Cell Niches, and Disease Relevance.” Stem Cells Translational Medicine (2014).
Rios, Anne C., et al. “In Situ Identification of Bipotent Stem Cells in the Mammary Gland.” Nature, v.506/7488 (2014).
Roy, Somdutta, et al. “Rare Somatic Cells From Human Breast Tissue Exhibit Extensive Lineage Plasticity.” Proceedings of the U.S. National Academy of Sciences, v.110/12 (2013).
Breast Cancer
Breast Cancer
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Breast Cancer
Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas, while those originating from lobules are known as lobular carcinomas. Breast cancer can occur in both men and women, but most of them occur in women. Breast cancer screening harms and benefits are controversial, but it is generally started at the age of 50 years in all women. Surgery is the most effective treatment for breast cancer. Chemotherapy and hormonal therapy also play a role in treatment. Radiation is used after breast-conserving surgery to prevent relapses. Hormonal receptors play an important role in pathogenesis and the treatment of breast cancer. Estrogen receptors, progesterone receptors, and HER2/neu receptors all are known to be expressed by most types of breast cancers, and the breast cancers that do not express these receptors are called triple negative breast cancers and they show resilience to all sorts of treatments.
Breast Development and Anatomy
Human breast development is a progressive process that is initiated during embryonic life. The glandular maturation occurs at puberty, while full breast differentiation is attained only with subsequent pregnancy and lactation. Breast tissue is composed of both epithelial and stromal elements. The epithelial components are branching ducts that connect the structural and functional units of the breast (the lobules) to the nipple. The stroma, which comprises the majority of the breast volume in the nonlactating state, is composed of adipose and fibrous connective tissue. The principal blood supply of the breast is derived from the internal mammary artery. Approximately one-third of the blood supply (mainly to the upper outer quadrant) is provided by the lateral thoracic arteries. Lymph flow from the deep subcutaneous and intramammary vessels moves centrifugally toward the axillary lymph nodes.
Types of Breast Cancer
In situ breast cancer refers to cancer in which the cells have remained within their place of origin—they have not spread to breast tissue around the duct or lobule. One type of noninvasive cancer called ductal carcinoma in situ (DCIS) is considered a precancerous lesion. This means that if it were left in the body, DCIS could eventually develop into an invasive cancer. Another type of noninvasive cancer called lobular carcinoma in situ (LCIS) is not considered precancerous because it won’t eventually evolve into invasive cancer. LCIS does, however, increase the risk of cancer in both breasts.
Invasive (infiltrating) breast cancers spread outside the membrane that lines a duct or lobule, invading the surrounding tissues. The cancer cells can then travel to other parts of your body, such as the lymph nodes. The type of tissue where breast cancer arises determines how the cancer behaves and what treatments are most effective. Parts of the breast where cancer begins include:
Figure 1 Anatomy of the human female breast
Source: Medline Plus.