Abstract
Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed.
Highlights
As highlighted throughout this special issue, cancer cells develop mechanisms of response to conditions of stress to evade death and support tumour progression
BRAF inhibitor resistant melanoma cells were shown to activate a novel truncated form of anaplastic lymphoma kinase (ALK), which was secreted in extracellular vesicles (EVs) that were capable of transferring drug resistance through activation of the mitogen-activated protein kinase (MAPK) signalling pathway in recipient cells [16]
Content of EVs released by gastric tumour-associated macrophages (TAMs) was altered following cisplatin treatment [30], with increased EV-miR21 transferred to recipient gastric cancer cells, suppressing apoptosis and activating the PI3K/AKT signalling pathway through down regulation of PTEN [30]
Summary
As highlighted throughout this special issue, cancer cells develop mechanisms of response to conditions of stress to evade death and support tumour progression. These mechanisms support escape from apoptosis, endoplasmic reticulum (ER) stress, autophagy, hypoxia, anti-cancer therapies, heat stress and chemical stress. Metalloproteinase-1 (MMP1) expression in ovarian cancer is linked with poor prognosis and was found to be packaged into EVs and transferred to the mesothelial cells [7] Studies such as these support the hypothesis that changes in cell phenotype during conditions of stress and development of resistance to therapy may result in a change in EV cargo and pattern of release. EV release into the circulation raises potential for use as circulating biomarkers reflecting changes in microenvironmental conditions and predicting response to therapy [5]
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