“…A current paucity of stem cell markers for many tissue lineages prevents geneology tracing to determine the cellular origin of cancer stem cells, making the functional in vivo self-renewal assay the most reliable currently available (Clarke et al, 2006). Tumor sphere formation, such as neurospheres for BTSCs, provides a powerful tool for the study of cancer stem cell self-renewal in culture, but care must be taken in the interpretation of these results because the in vitro assay may or may not be selecting the cancer stem cells (Clarke et al, 2006) and is a phenomenon that does not occur in vivo (Chaichana et al, 2006). Even the term tumor initiating cell can lead to confusion, as cancer stem cells may not actually initiate tumors but be stimulated to neoplastic transformation by environmental insults (Clarke et al, 2006).…”