Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self
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(2020) 40:33
Inflammation and Regeneration
REVIEW
Open Access
Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self-advantageous niche microenvironments Tetsuya Taga* and Kouichi Tabu*
Abstract 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. Keywords: Autoschizis-like products, Cancer stem cell, Glioma, Glioma stem cell, Polymer, Stem cell niche, Tumorassociated macrophage
Background Malignant gliomas are the most frequent primary brain tumors in adults, and despite the progress of treatments including surgical resection and chemo/radiotherapies, the survival outcome has not been improved and far from desired [1]. According to the WHO criteria, * Correspondence: [email protected]; [email protected] Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU) , 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
glioblastoma, also known as glioblastoma multiforme or GBM, is the most malignant glioma classified as grade IV. Highly tumorigenic cancer stem cells (CSCs), due to their responsibilities for tumor progression, recurrence after conventional chemo/radiotherapies, and metastasis, have been proposed as a promising target for cancer eradication [2]. In order to tackle the therapeutic difficulties of cancers involving CSCs, much attention has focused on the extracellular microenvironments of CSCs, i.e., CSC niche, which is considered to maintain
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