Signaling Factors Involved in Self-Renewal of Breast Cancer Stem-like Cells

Postoperative or post-treatment survival is greater among breast cancer patients than among those with other types of cancer. However, recurrence and metastasis to the bones, 1 lungs, and brain are possible after a latent period of 5–10 years. Various reports suggested that the cancer stem-like cells (CSC) are found in breast cancer and are considered to deter 2–5 the prognosis of events including tumor recurrence and metastasis. Tumors are speculated to comprise a heterogeneous cell population constituted by CSC, transit-amplifying (TA) cells, 6,7 and terminally differentiated cells. CSC can undergo self-renewal, symmetric cell division, and can yield terminally differentiated cells and somatic stem cells via asymmetric cell .8,9 division In this heterogeneous cell population, CSC, a small cell population, occupies the highest position in tumor hierarchy. With slow cell cycles and high anti-oxidative capacity compared with non-CSC, CSC are resistant to conventional chemoand radiotherapy 10–12 targeting proliferating cancer cells. Despite large cancer cell populations being eliminated through chemotherapy, only a few CSC may survive and cause tumor recurrence and metastasis. Hence, it is essential to elucidate the characteristics of CSC and standardize methods of assessing CSC-enriched populations and associated culture methods. Flow cytometry analysis using known CSC-specific antibodies is a popular and simple method for 13–15 assessing CSC. The CSC population can be enriched and fractionated through flow cytometry analysis because cell membrane characteristics of CSC is analyzed in only living cells. In standardizing culture methods for CSC, tumor sphere culture and organoid culture 16,17 are useful tools to assess the self-renewal capacity of CSC in vitro. Sphere culture has 18 been used to assess the survival and self-renewal capacity of neural stem cells in culture. Abstract