Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self-advantageous niche microenvironments

Due to the nature of enhanced resistance to conventional chemo/radiotherapies and metastasis, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for cancer eradication. To tackle the therapeutic difficulties of cancers involving CSCs, extensive research efforts have been directed toward understanding the extracellular microenvironments of CSCs, i.e., CSC niche, which plays important roles in CSC maintenance and expansion. Here we review recently identified mechanisms of maintenance and expansion of glioma CSCs (GSCs) leading to glioma progression and recurrence, with particular emphasis on the reports made by studies with a unique approach using polymer microarrays screening and with a unique viewpoint of necrotic particles. The polymer-based approach identified two groups of niche components, extracellular matrices (ECMs) and iron, and uncovered that co-expression of ECM-, iron-, and macrophage-related genes is predictive of glioma patients’ outcome. The study in view of a unique fraction of GSC-derived necrotic particles proposed that such particles develop GSC-supportive tumor-associated macrophages (TAMs). Taken together, these studies provide new insights into the mechanisms underlying GSC-driven niche development, i.e., organization of the self-advantageous niche microenvironments for GSC maintenance and expansion leading to glioma progression and recurrence. A series of such studies can redefine the current concept of anti-GSC niche therapy that targets ligands/receptors supporting GSCs, and have potential to accelerate cancer therapy development.