In the September 13th issue of Cell Stem Cell, P. C. Herman et al. from Ludwig-Maximilians University in Munich, Germany reported their findings on the identification of cancer stem cells in human pancreatic adenocarcinoma. The authors noted that pancreatic cancers are the fourth leading cause of cancer-related deaths. The investigators identified in human pancreatic cancer tissues a subpopulation of cancer stem cells that were CD133+, CXCR4+. This subpopulation of stem cells were found to be highly tumorigenic and resistant to chemotherapy. By depleting the cancer stem cell pool of these cells, the researchers discovered that they were able to abrograte the cancer stem cells' metastatic and tumorigenic potential. The authors concluded that this subpopulation of migrating CD133+.,CXCR4+ cells were essential for tumor metastatsis. It was also proposed that strategies to block the ligand SDF-1 and its receptor, CXCR4, may have important future clinical applications in treating cancer metastasis.

Scientists from Columbia University Medical College, I. Matushansky et al., published in the October 18th online edition of J. Clinical Investigation their findings on human mesenchymal stem cells (hMSCs) and the molecular mechanisms that cause them to give rise to malignant fibrous hisiocytoma (MFH). This form of cancer is now referred to as high-grade undifferentiated pleomorphic sarcoma in humans. The investigators found that they were able to generate progenitors of MFH by inhibiting the Wnt signaling pathway (via overexpressing its inhibitor, DKK1, in hMSCs). Using siRNA knockdown, recombinant proteins, and antibody neutralization, the researchers presented evidence that DKK1 inhibits differentiation of hMSCs. Additionally, inhibiting Wnt2/β-catenin signaling blocks hMSC commitment to differentiation, which can eventually lead to transformation. The investigators showed that they were able to form MFH-like tumors when the mesenchymal-blocked stem cells were transplanted into immunocompromised nude mice. The authors concluded that their results provide "mechanistic insights" on the cells forming MFH" as well as showing a tumor suppressor role for Wnt signaling.

In the October 11th issue of Cell Stem Cell, M. Todaro et al. from the University of Palermo, Italy, reported their findings on the identification and characterization of human colon cancer stem cells using the stem cell marker, CD133. From human colon carcinomas, the investigator isolated a subpopulation of stem cells in the tumors that were CD133+. These cells represented approximately 2% of the cells in the colon cancer. The researchers were able to cultivate the cells as undifferentiated tumor spheroid bodies in order to initiate tumor growth in immunodeficient mice. In the xenografts, the investigators confirmed that CD133+ were the cancer-initiating cells which gave rise to tumors resembling the original human phenotype along with the rare tumorigenic CD133+ in the grafts. It was found that the cancer stem cells produced IL-4 and utilized the cytokine to protect against apoptosis. Consequently, treating the cancer stem cells with an IL-4 receptor antagonist or neutralizing antibodies enhanced the anti-tumor effect of standard chemotherapeutic drugs. The authors concluded that selective sensitization of the CD133+ cells by blocking the activity of IL-4 suggests a novel therapeutic regimen for treating colon cancers. The authors also suggested that "colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4."

V. K Gadi and J. L. Nelson from the Fred Hutchinson Cancer Research Institute in Seattle, Washington, reported in the October 1st issue of Cancer Research the results of their study on fetal microchimerism in breast cancer patients. Fetal microchimerism (FMc) is a condition when residual fetal cells are found in women following a pregnancy. The study involved 82 women of which 35 had breast cancer and 47 were healthy and who gave birth to a son. The women's peripheral blood were analyzed for Y chromosome-specific gene DYS14 using real-time quantitative PCR. The study results showed that FMc was found more frequently in healthy women than in women with breast cancer (43% vs 14%). Statistical analysis of the data using odds ratios showed a highly significant correlation (p=0.01).