Extracellular Vesicles and the Inflammasome: An Intricate Network Sustaining Chemoresistance

Mezzasoma, Letizia; Bellezza, Ilaria; Romani, Rita; Talesa, Vincenzo Nicola

doi:10.3389/fonc.2022.888135

Cited by 3 publications

(2 citation statements)

References 87 publications

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“…Physiologically, EVs are mediators of intercellular communication, while pathologically, they are involved in the initiation, exacerbation, and resistance in various diseases [ 280 ]. This leads to a large proportion of unsuccessful treatment regimens, specifically in cancer, due to the role of EVs in conferring resistance to cancer cells, via immune evasion and metastasis, as well as to chemotherapy [ 281 , 282 ].…”

Section: Pharmacology Of Extracellular Vesiclesmentioning

confidence: 99%

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Al-Jipouri,

Eritja,

Bozic

2023

IJMS

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Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs’ biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes.

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Section: Pharmacology Of Extracellular Vesiclesmentioning

confidence: 99%

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Al-Jipouri,

Eritja,

Bozic

2023

IJMS

View full text Add to dashboard Cite

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“…While these findings show how inflammasome affects EVs secretion, it is worthy to note that EVs can also influence inflammasome activity, thus revealing a bidirectional crosstalk. Hence, EVs can either positively or negatively affect inflammasome activity depending on the nature of the EVs releasing cells ( 148 ). Exosomes from LPS-treated macrophages are able to activate NLRP3 inflammasome in AML-12 hepatocytes ( 149 ).…”

Section: Linking Nf-κb and Evs Activity In Cancer Progression And The...mentioning

confidence: 99%

EV-Mediated Chemoresistance in the Tumor Microenvironment: Is NF-κB a Player?

et al. 2022

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Drug resistance is a major impediment to patient survival and remains the primary cause of unsuccessful cancer therapy. Drug resistance occurs in many tumors and is frequently induced by chemotherapy which triggers a defensive response both in cancerous and cancer-associated cells that constitute the tumor microenvironment (TME). Cell to cell communication within the TME is often mediated by extracellular vesicles (EVs) which carry specific tumor-promoting factors able to activate survival pathways and immune escape mechanisms, thus sustaining tumor progression and therapy resistance. NF-κB has been recognized as a crucial player in this context. NF-κB activation is involved in EVs release and EVs, in turn, can trigger NF-κB pathway activation in specific contexts, based on secreting cytotype and their specific delivered cargo. In this review, we discuss the role of NF-κB/EVs interplay that sustain chemoresistance in the TME by focusing on the molecular mechanisms that underlie inflammation, EVs release, and acquired drug resistance.

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HSP27/IL-6 axis promotes OSCC chemoresistance of cisplatin, migration and invasion by orchestrating macrophages via a positive feedback loop

Qi,

Cao,

Jiang

et al. 2024

Preprint

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The mechanisms of interaction and crosstalk between tumor cells and tumor-associated macrophages (TAMs) have provided novel options for intervening in tumor progression. However, the molecular mechanisms of the interaction between the tumor cells and TAMs underlying oral squamous cell carcinoma (OSCC) invasio, migration and chemoresistance remain unclear. This study sought to specifically investigate the role of the tumor-cell-derived paracrine heat shock protein 27 (HSP27) in OSCC invasion, migration and chemoresistance and the potential molecular mechanisms of the interaction between the tumor cells and TAMs. In this study, bioinformatic analysis and IHC results demonstrated that the expression level of HSP27 was higher in the tissues of patients with advanced lymph node metastasis of OSCC than that in early stage non-metastatic patients, and that its expression level was positively correlated with the levels of multidrug resistance-associated proteins and macrophage infiltration. In vivo, Survival of low-expressing HSP27 xenograft model mice was inferior to that of controls. In vitro, TAMs-CM significantly up-regulated the expression level of HSP27 in the two types of OSCC tumor cells including CAL27 and SCC9 cells. The OSCC tumor cell-derived HSP27 regulated TAMs through paracrine mode and reduced the level of apoptosis induced by the chemotherapeutic drug cisplatin in tumor cells, thus promoting chemoresistance in OSCC. HSP27 promoted the secretion of cytokine IL-6 from TAMs, whereas TAMs-derived IL-6 up-regulated the expression of HSP27 and enhanced the chemoresistance, migration and invasion of OSCC in tumor cells through an autocrine mode and activates the β-catenin pathway during this process, additionally up-regulated the stem cell properties of tumor cells through an autocrine manner. Tumor-cell-derived paracrine HSP27 promoted OSCC invasion and migration through enhancing the epithelial–mesenchymal transition (EMT) of tumor cells via binding to toll-like receptor 4 (TLR4) on the surface of the TAMs. HSP27/TLR4 induced polarization of the TAMs to an M2-like phenotype and the secretion of IL-6 in the TAMs. Respectively, TAMs-derived IL-6 enhanced OSCC invasion and migration via autocrine HSP27/TLR4 signaling in tumor cells while IL-6 promoted the EMT of tumor cells via autocrine HSP27. Collectively, tumor-cell-derived paracrine HSP27 promoted OSCC migration, invasion and chemoresistance by orchestrating macrophage M2 polarization and IL-6 secretion from macrophages via a positive feedback loop. TAM-derived IL-6 enhanced these progressions via autocrine HSP27/IL-6 signaling in tumor cells. Targeting HSP27/IL-6 may be an effective treatment strategy for OSCC patients, and it is expected to control OSCC progression and improve its prognosis and recurrence in patients.

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Extracellular Vesicles and the Inflammasome: An Intricate Network Sustaining Chemoresistance

Cited by 3 publications

References 87 publications

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

EV-Mediated Chemoresistance in the Tumor Microenvironment: Is NF-κB a Player?

HSP27/IL-6 axis promotes OSCC chemoresistance of cisplatin, migration and invasion by orchestrating macrophages via a positive feedback loop

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