During their investigation into the mechanism(s) of self-renewal in both normal and cancer stem cells, C. Zhao et al. from Duke University Medical Center reported in the December 11th issue of Cancer Cell on the role of Wnt signaling in regulating self-renewal of hematopoietic progenitors. With transgenic mice deficient in β-catenin in hematopoietic stem cells (HSCs), the investigators found that the mice were able to generate HSCs, but lack the ability in vitro for long-term growth and maintenance. Additionally, the mice lack the ability to form chronic myelogenous leukemia (CML) when they were infected with the oncogene, BCR-ABL. However, it was noted that the transduced mice were able to progress to acute lymphocytic leukemia (ALL). The authors concluded that their studies demonstrate that Wnt signaling is required for self-renewal in both normal and cancer stem cells of the hematopoietic system in mice.

Chinese investigators from Sun-Yat -Sen University, F. Yu et al., reported in the December 14 issue of Cells their findings on identifying a miRNA, let-7, that appears to have a regulatory role in self-renewal and tumorigenicity of tumor-initiating cells (BT-IC) found in human breast cancer patients. In comparing the expression of let-7 in differentiated cells from breast cancers cell lines, BT-IC, and cells from non-BT-IC, the researchers found that the expression of let-7 was markedly reduced in the BT-IC population. Transfecting the BT-IC with let-7-lentivirus caused the infected cancer stem cells to differentiate concomitant with a decrease in both their ability to proliferate and to form 3-D mammosphere in vitro. In vivo studies, the investigators found that the infected BT-IC also lost their ability to form tumors as well as metastatic potential in NOD/SCID mice. Conversely, antagonizing let-7 with anti-sense oligonucleotides resulted in increased proliferation and self-renewal of non-tumor-initiating cells. The investigators also found let-7 switched off two oncogenes in the BT-IC, Ras and HMG2A. Silencing H-Ras in the BT-IC reduced their ability to self-renew, but not their ability to differentiate. On the otherhand, silencing HMGA2 enhanced differentiation, but did affect the BT-IC to self renew. The authors concluded that let-7 regulates both self-renewal and differentiation in cancer stem cells. The authors also speculated that let-7 may have therapeutic value in treating breast cancers in the future.

At the 30th Annual San Antonio Breast Cancer Symposium, investigators D. A. Berry et al. from the M.D. Anderson Cancer Center, yesterday presented the results of their retrospective study on high-dose chemotherapy and autologous stem cell transplantation in women with primary breast cancers (having involved at least 4 axillary lymph nodes). With meta-analysis, the study comprised 15 known randomized trials around the world from 1988 to 2002. By adjusting the study for demographics, clinical characteristics, intensity of therapy, and estrogen receptor status, the investigators found that in the 6,210 patients there was very little survival benefit when treated with this form of adjuvant therapy. The medium patient age was 46 years, who had a median follow-up of 6 years. The authors concluded that what they had learned from the study was that "the doses used in standard chemotherapy regimens for advanced breast cancer had reached a plateau and that increasing beyond that dose is not delivering a greater benefit. It is likely that there are patients who respond to a specific chemotherapy type. Once one give enough of that chemotherapy to benefit those patients, there's no advantage from additional treatment."