Cancer stem cells: cell culture, markers, and targets for new therapies

Abstract

A cancer stem cell (CSC) is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in CSC culture, but tumor cell heterogeneity has made purification of CSCs difficult. Indeed, it may be that CSCs significantly vary from tumor to tumor. We also discuss the proposal that CSCs are resistant to radiotherapy and chemotherapy and play a major role in repopulating tumors following treatment. To overcome their resistance to conventional therapies, we may be able to use our extensive knowledge of the signaling pathways essential for stem cells during development. These pathways have potential as targets for new glioblastoma therapies. Hence, although there is an ongoing debate on the nature of CSCs, the theory continues to suggest new ideas for both the lab and the clinic.

Fig. 1

Proposed lineage for glioma CSCs. The CSCs (red) cultured in defined medium express stem cell markers, some of which are listed. CSCs may not express all of these markers and may vary from tumor to tumor. The CSCs differentiate to transit-amplifying cells. Expression of stem cell markers is decreased in the transit-amplifying cells (blue), but there are no distinct markers that are upregulated in the transit-amplifying cells. As the spheres mature, a few of the transit-amplifying cells differentiate to astrocytic cells and, to a lesser degree, neuronal and oligodendrocytic markers (astrocytic cells = green). With the adherent laminin cell culture system, stem cell marker expression is enhanced, suggesting that the fraction of CSCs is increased. Also, there are almost no astrocytic cells. Treatment with serum rapidly and efficiently induces astrocytic differentiation.