Abstract
Simple SummaryThis paper summarizes the crosstalk between tumor/non-tumor cells and other elements of the glioblastoma (GB) microenvironment. In tumor pathology, glial cells result in the highest number of cancers, and GB is considered the most lethal tumor of the central nervous system (CNS). The tumor microenvironment (TME) is a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be a key factor for the ineffective treatment since the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. A deeper understanding of cell–cell interactions in the TME and with the tumor cells could be the basis for a more efficient therapy.The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell–cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.
Highlights
IntroductionThe central nervous system (CNS) evolved in an integrated network composed of neurons (decisional cells) and neuroglial cells (homeostatic, immuno-, and activity modulators) [1,2]
The central nervous system (CNS) evolved in an integrated network composed of neurons and neuroglial cells [1,2]
tumor microenvironment (TME) is a complex peritumoral hallo composed of tumor cells and several non-tumor cells, occasionally prevalent [9]
Summary
The central nervous system (CNS) evolved in an integrated network composed of neurons (decisional cells) and neuroglial cells (homeostatic, immuno-, and activity modulators) [1,2]. Upon activation, these cells are responsible for the secretion of a substantial number of inflammatory factors: cytokines, matrix metalloproteinases—MMP, growth and oxidative stress factors, that will suppress or activate the signaling pathways, modifying their beneficial tissular action and promoting tumor development and invasion [11,12]. Similar mechanisms as in physiological communication are used, including either direct exchanges (via extracellular vesicles—EVs, gap junctions—GJs, ion channels, and transporters), or soluble factors (neurotransmitters, hormones, cytokines/chemokines, growth factors) [15]. Through all these factors, adjustments, and disruptions of the phenotype of vicinal and even distant cells are achieved [15].
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