Stem cell-like cancer cells in cancer cell lines

Abstract

There is increasing evidence that malignant tumors, such as leukemia, breast cancers, and brain cancers, contain cells that maintain the characteristics of tissue-specific stem cells and are malignant. Malignant glioma, for example, contain both proliferating cells expressing stem cell markers and differentiating cells expressing either neuronal markers or glial markers, raising the possibility that the tumors may contain neural stem cell (NSC)-like cells. This idea is supported by recent findings that malignant glioma can be generated from both NSCs and glial lineage cells, such as oligodendrocyte precursor cells or astrocytes, which behave as NSC-like cells in appropriate conditions. Additional evidence also exists indicating that malignant tumors might contain stem cell-like cancer cells, called &lquo;cancer stem cells&rquo; (CSCs). Although a number of anti-cancer drugs and irradiation have been successful in eliminating cancers, some cancer cells survive and the cancer recurs, indicating that the surviving cells are not only resistant to such anti-cancer drugs and irradiation but are also malignant. Previous studies have shown that various ATP binding cassette transporters, such as the protein encoded by the multi-drug resistant protein and the breast cancer resistant protein 1 (BCRP1), contribute to drug resistance in cancers. Interestingly, some of these transporters are also expressed in many kinds of normal stem cells. BCRP1, for example, excludes the fluorescent dye Hoechst 33342, identifying a side population (SP), which is enriched for stem cells. Together, these findings suggest that cancers might contain an SP that is enriched for cells that have the characteristics of CSCs. Taking advantage of the common characteristics between stem cells and cancer cells, several groups have demonstrated that such stem cell-like cancer cells, although not other cells, in tumors or cancer cell lines can self-renew, express well-known stem cell markers such as CD133, and form tumors when transplanted in vivo, suggesting that tumors contain CSCs and that stem cells might be the primary target of tumorigenesis. In order to develop effective therapy against tumors, characterizing and finding ways to kill CSCs is essential.