The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.
Background: It is widely known that prenatal stress (PS) exposure causes depression-like behaviour to offspring, as well as maladaptive responses including neurobiological and physiological changes. Glutamate neurotransmission was recently impaired in the action of PS and in antidepressant mechanisms, but little is understood about the mechanisms underlying this consequence. In the synapse, vesicular docking and neurotransmitter release requires the formation of the soluble Nethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Impairments in vesicle docking, and alterations in SNARE complex formation are associated with impaired neurotransmitter release. Methods: To examine the effect of PS on the SNARE complex, pregnant rats were assigned to Control group (CON) and PS group (PS). PS rats were exposed to restraint stress on days 14-20 of pregnancy three times daily for 45min. Results: Immunoblotting of the hippocampal and prefrontal cortex homogenates revealed significantly increased SNARE complex formation (P<0.05). For the offspring, the SNARE protein SNAP-25, VAMP-2 and syntaxin 1a protein expression were significantly increased in the hippocampus and prefrontal cortex (P<0.05), associated with increased Munc-18, alpha-synuclein, CSP-alpha, complex1 and complex2, which chaperone SNARE-complex formation (P<0.05). Conclusion: Increased SNARE complex and three SNARE protein of PS may explain the increase of glutamate in synaptic cleft and its downstream excitotoxicity.
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