cells are sandwiched between the stroma and luminal cells in breast tissue. They are frequently found in the glandular epithelium and are involved in expelling secretions from the exocrine glands.
Adipose-Derived Stem Cells (ASCs)
As discussed earlier, adipose tissue is composed of adipocytes, or fat cells. ASCs have remarkable plasticity and have the ability to differentiate into several different cell types, including adipocytes, cardiomyocytes, chondrocytes, epidermal cells, endothelial cells, hepatocytes, myocytes, osteoblasts, cells similar to glial cells, and cells similar to neurons.
These characteristics make ASCs a very useful type of stem cell. Furthermore, ASCs have shown the ability to differentiate into cells with angiogenic characteristics since they are derived from the stromal vascular fraction. The stromal vascular fraction of adipose tissue is the important portion because it contains a significant amount of preadipocytes, mesenchymal stem cells, endothelial progenitor cells, and immune cells such as T-cells, B-cells, mast cells, and macrophages. Also, ASCs have been identified as cells that secrete growth factors such as insulin-like growth factor (IGF), hepatocyte growth factor (HGF), pro-angiogenic growth factor, and vascular endothelial growth factor (VEGF). These characteristics of ASCs make them extremely valuable tools for regenerative medicine.
Mesenchymal Stem Cells (MSCs)
Mesenchymal stem cells have the ability to differentiate into osteoblasts, chondrocytes, myocytes, neurons, and adipocytes. MSCs are derived from mesoderm, which forms connective tissue in the body. However, the MSCs in breast tissue are derived from breast adipose tissue. These MSCs work to stimulate the growth of tumor cells in breast cancer, and can make the disease metastasize. MSCs play a role in basal-type cancer by degrading the extracellular matrix and facilitating the invasion of basal-like cancer cells. Further research on the role of MSCs in breast cancer progression should be performed.
Krishna S. Vyas
Tyler Guidugli
University of Kentucky College of Medicine
See Also: Breast: Development and Regeneration Potential; Breast: Existing or Potential Regenerative Medicine Strategies; Breast: Major Pathologies.
Further Readings
Cell potency. In Wikipedia, The Free Encyclopedia. http://en.wikipedia.org/w/index.php?title=Cell_potency&oldid=607501144 (Assessed May 10, 2014).
Cell Press. “‘Basal-Like’ Breast Cancer Does Not Originate From Basal Stem Cells.” ScienceDaily (September 6, 2010). http://www.sciencedaily.com/releases/2010/09/100902121043.htm (Accessed May 13, 2014).
Kim, J., L. Escalante, B. Dollar, et al. “Comparison of Breast and Abdominal Adipose Tissue Mesenchymal Stromal/Stem Cells in Support of Proliferation of Breast Cancer Cells.” Cancer Investigation, v.31/8 (2013). doi:10.3109/07357907.2013.830737
Philips, B. J., K. G. Marra, and J. P. Rubin. “Healing of Grafted Adipose Tissue: Current Clinical Applications of Adipose-Derived Stem Cells for Breast and Face Reconstruction.” (2014). Wound Repair & Regeneration, v.221 (2014).
Breast: Current Research on Isolation or Production of Therapeutic Cells
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Breast: Current Research on Isolation or Production of Therapeutic Cells
In 2012, breast cancer was the second most commonly diagnosed cancer worldwide with an approximate 1.7 million diagnoses (11.9 percent of new cancer diagnoses). Breast cancer is the result of a deregulated biological process in which normal breast cells have been transformed and are able to self-renew indefinitely. The application of stem cells to breast cancer is twofold. First, the study of stem cells has led to greater understanding of cancer cell biology and the concept of the cancer stem cell (CSC). Second, stem cell research has led to insights into the development of breast tissue and the molecular mechanisms leading to breast cancer, which has provided new targets and potential treatment modalities for breast cancer.
Role of Breast Cancer Stem Cells
It is a small population of transformed cells that serve as the nidus for a breast tumor. Furthermore, it is the additional abilities of these transformed cells to migrate to other sites and to enter quiescence (dormancy) that make them terribly difficult to eradicate. It is these cells within breast tumors, breast CSCs, which have stem-cell like features and have acquired the capacity to proliferate in an uncontrolled manner.
Researchers have determined that breast CSCs tend to migrate to bone marrow, where they can become dormant. After they have entered the bone marrow, breast CSCs can reside among the stromal cells and maintain dormancy or reverse their dormancy to establish metastases. Both dormancy and resurgence are cell states supported by the microenvironment and intracellular signaling with surrounding mesenchymal stromal cells in the bone marrow. Breast CSCs are capable of re-establishing breast cancers after treatment (chemotherapy and radiation) and apparently successful remission.
Breast Cancer Stem Cells: A Potential Treatment Target
In addition to their role in tumor resurgence, breast CSCs play a role in resistance to therapy, as suggested by current research. Researchers are investigating those molecular mechanisms and signaling pathways that transform healthy breast cells to breast CSCs, and the surface markers and signaling pathways specific to breast CSCs. Several breast CSC cell-surface markers have been suggested that are not limited to CSCs; the goal of targeted therapy is to attack breast CSCs without harm to normal breast cells.
In 2003, researchers at the University of Michigan Cancer Center (UMCC) discovered the existence of breast CSCs. Since then, scientists and clinicians have published their ongoing research findings on breast CSCs that have the potential for high impact on the treatment of breast cancer. One finding by the researchers at UMCC is mutation of the HER2 and PTEN genes stimulates cell division and self-renewal in breast CSCs. After being triggered, the breast CSCs begin to proliferate and invade the surrounding breast tissue. Scientists at UMCC experimented by treating cells with drugs that would inhibit HER2 and PTEN; this resulted in a reduction in the growth of these cells.
Researchers at UMCC have identified a receptor molecule found on the surface of breast CSCs that triggers abnormal cell growth in response to tissue inflammation and chemotherapy. When this receptor molecule is blocked, breast cancer cells die. This research has only been performed in a rat model of breast cancer and thus requires further studies in the clinical setting. Another finding is that mesenchymal stem cells (MSCs) found in bone marrow are involved in breast cancer development. In a study performed in mice, the researchers found that breast tumors sent out molecular signals to the MSCs to leave bone and enter the tumor. After entering the tumor, the MSCs sent signals to the breast CSCs, stimulating them to divide.
In addition, researchers at UMCC determined that components of nutrition may work to inhibit breast CSCs. In studies performed
