Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle distribution and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24þ sub-population possessed stem celllike characteristics of remaining quiescence and more chemoresistant compared with CD24À fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 Â 10 3 CD24 þ cells was able to form tumor xenografts in nude mice, whereas equal number of CD24 À cells remained nontumorigenic. We also found that CD24 þ cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, b-catenin, Bmi-1, Oct4, Oct3/4, Notch1 and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24 À cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

SummaryFibroblasts were extracted from tissue in tumor burden zones, distal normal zones and interface zones between tumor and normal tissue of human breast carcinomas, and the corresponding fibroblasts were designated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). The crosstalk between three types of fibroblasts and breast cancer cells was evaluated using an in vitro direct co-culture model. We found that INFs grew faster and expressed higher levels of fibroblast activation protein than did NFs and CAFs. Compared with CAFs and NFs, INFs grown with breast cancer cells were significantly more effective in inducing an epithelial-mesenchymal transition (EMT) in cancer cells, as indicated by induction of vimentin and N-cadherin and downregulation of E-cadherin. This EMT process was also accompanied by activation of extracellular signal-regulated kinase (ERK) and modulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) expression. Additionally, INFs promoted breast cell migration to a larger extent compared with NFs and CAFs. Taken together, these findings indicate that INFs isolated from the tumor interface zone exhibited more robust biological modulatory activity than did NFs and CAFs isolated from normal and tumor zones of the same tumor tissue, suggesting that the interface zone of the tumor represents a dynamic region vital to tumor progression.

Temperature-programmed desorption experiments show that acetone chemisorbs on nanotubes while physisorption occurs on graphite. Computed high binding energies for chemisorption using hybrid quantum mechanical and semiempirical calculations are in good agreement with the experimental thermal desorption data. The strong chemical interactions between acetone and the nanotube surface are established as being due to the effects of curvature and topological defects.

The design and development of new pyrene-based fluorescent probes, P-Hcy-1 and P-Hcy-2, which display selective fluorescence enhancements in response to homocysteine (Hcy), are described. The distinctly different fluorescence responses of P-Hcy-1 and P-Hcy-2 to Hcy vs. Cys are explained by theoretical calculations. Finally, the results of cell experiments show that these probes can be used to selectively detect Hcy in mammalian cells.