Making of glioma-initiating cells

Abstract

There is an increasing body of evidence that suggests that malignant tumors, such as leukemia, breast cancers, and brain cancers, contain cells that maintain the characteristics of tissue-specific stem cells (TSSCs) and are malignant. Malignant gliomas, for example, contain proliferating cells expressing neural stem cell (NSC) markers, such as nestin and CD133, and differentiating cells expressing either neuronal markers or glial markers, raising the possibility that the tumors may contain NSC-like cancer cells. Additional evidence also exists, which indicate that malignant tumors might contain stem cell-like cancer cells, called “cancer stem cells” (CSCs) or “tumor initiating cells”. Although a number of anti-cancer drugs and irradiation therapy have been successful in eliminating cancers, occasionally some cancer cells survive and invade other tissues, leading to the recurrence of cancer; this indicates 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 multi-drug resistant protein encoded by the multi-drug resistant gene, and the breast cancer resistant protein 1 (BCRP1), contribute to drug resistance in cancers. Interestingly, some of these transporters are also expressed in many types of normal stem cells. BCRP1, for example, excludes the fluorescent dye Hoechst 33342, identifying a side population (SP) enriched with TSSCs. Taking advantage of the common characteristics that exist between TSSCs and cancer cells, many groups have demonstrated that CSCs in tumors or cancer cell lines can self-renew, express well-known TSSC markers, form tumors when transplanted in vivo and show resistance to anti-cancer treatments; this suggests that CSCs are important targets for curable therapy. In order to develop an effective therapy against tumors, characterizing and finding ways to kill CSCs is essential. In this review, I have summarized the recent progresses made in glioma CSC research and discuss the perspectives of this field.