Global Profiling of Signaling Networks: Study of Breast Cancer Stem Cells and Potential Regulation

Microarray analysis was used to examine gene expression profiles in breast cancer stem cells in an attempt to identify signature patterns and mechanisms of signaling networks in these cells

Melanoma-initiating cells: a compass needed

Most tumours contain a heterogeneous population of cancer cells, which harbour a range of genetic mutations and have probably undergone deregulated differentiation programmes that allow them to adapt to tumour microenvironments. Another explanation for tumour heterogeneity might be that the cells within a tumour are derived from tumour-initiating cells through diverse differentiation programmes. Tumour-initiating cells are thought to constitute one or more distinct subpopulations within a tumour and to drive tumour initiation, development and metastasis, as well as to be responsible for their recurrence after therapy. Recent studies have raised crucial questions about the nature, frequency and importance of melanoma-initiating cells. Here, we discuss our current understanding of melanoma-initiating cells and outline several approaches that the scientific community might consider to resolve the controversies surrounding these cells

CD133 expression predicts for non-response to chemotherapy in colorectal cancer

10.1038/modpathol.2009.181Modern Pathology233450-457MODP

Characterization and Propagation of Tumor Initiating Cells Derived from Colorectal Liver Metastases: Trials, Tribulations and a Cautionary Note

Tumor initiating cells (TIC) are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHʰᶦᵍʰ populations were rare (0.4 and 0.3% for EPCAM⁺/ALDHʰᶦᵍʰ/CD133- and EPCAM⁺/ALDHʰᶦᵍʰ/CD133⁺ populations respectively) and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHʰᶦᵍʰ>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHʰᶦᵍʰ, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent heterogeneity observed in cancer populations is maintained