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
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 in mice, the researchers found that a compound found in broccoli, sulforaphane, killed breast CSCs and inhibited new tumors. Another interesting finding was that curcumin, a component of the Indian spice turmeric, decreased the number of breast CSCs that were able to grow in the laboratory. With the help of an international research team, scientists determined the transition between being in the epithelial and mesenchymal states (development states of the breast cancer cell) endows breast CSCs with the capacity for tissue invasion, dissemination, and metastasis.
These research findings provide significant avenues to exploit the use of stem cells as a treatment for breast cancer. One pathway is the use of monoclonal antibodies for the specific targeting of breast CSCs. Another pathway is to exploit the tropism between MSCs and breast CSCs. MSCs could be genetically modified and used to deliver drugs specifically to tumor cells. Studies performed in the laboratory have suggested the use of genetically modified MSCs to deliver therapy to breast cancer tumors. However, the mechanism has not been fully defined. To exploit these pathways, an in-depth understanding of signaling between normal cells and breast CSCs is required to minimize damage to healthy cells.
Use of Stem Cells in Breast Cancer Treatment
As noted, MSCs would be a good candidate to use as a modified stem cell to deliver breast CSC-specific chemotherapy. Lentiviral vectors have been used to modify MSCs without modifying cell-surface markers.
In addition to their ease of modification, MSCs are attracted to tissue injury by specific cytokines. MSCs play a role in tissue repair as part of their normal role in the body. MSCs migrate to tumors (since they damage the surrounding tissue) and could be exploited as drug transporters to specific tumor sites.
To date, stem cells have been used in clinical trials as supportive therapy to replenish blood cell development or to ameliorate other side effects of treatment for breast cancer.
Conclusion
During 2012, approximately 522,000 women died of breast cancer. Although the treatment of breast cancer has improved, breast cancer remains a leading cause of death. Stem cell research has elucidated