Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3

Li, Fēi; Xu, Ting; Chen, Peiling; Sun, Rui; Li, Chaoyi; Zhao, Xin; Ou, Jinxin; Li, Jingyao; Liu, Taoshu; Zeng, Maozhen; Zheng, Wei; Lin, Yunchen; Yang, Le; Li, Zecang; Chen, Haisheng; Zhang, Qing

doi:10.7150/ijbs.76162

Cited by 24 publications

(8 citation statements)

References 45 publications

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“…For instance, cell ferroptosis is suppressed in osteosarcoma by recombinant lysine specific demethylase 4A (KDM4A)-mediated demethylation of the solute carrier family 7 member 11 (SLC7A11) histone, which deepens the response to osteosarcoma, chemoresistance, and understanding of epigenetic regulatory mechanisms in metastasis ( 23 ). Also, inhibiting ferroptosis and promoting distant metastasis of nasopharyngeal cancer by upregulating integrin subunit beta 3 (ITGB3) are two effects of platelet-derived extracellular vesicles ( 24 ). Moreover, dysregulation of cholesterol homeostasis leads to resistance to ferroptosis, increasing cancer tumorigenicity and metastasis ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis

Zhou,

Xu,

et al. 2023

J Thorac Dis

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Background To identify the potential key genes of ferroptosis in the pathogenesis of lung cancer with bone metastasis (LCBM) by bioinformatics analysis to provide new targets for treating LCBM and an indicator for early monitoring. Methods We first obtained differentially expressed genes (DEGs) associated with ferroptosis from the Gene Expression Omnibus (GEO) database. MiRWalk 2.0 was used to predict the key microRNAs (miRNAs) and construct related gene-miRNA interaction networks. The functional enrichment analysis of key miRNAs was performed using the miEAA database. Finally, the clinical data of 105 lung cancer patients were retrospectively analyzed, and logistic regression analysis was conducted to assess the relationship between serum alkaline phosphatase (ALP), neuron-specific enolase (NSE), and bone metastasis in lung cancer patients, and a receiver operating characteristic (ROC) curve was drawn. Results We identified 15 ferroptosis-related genes that were differentially expressed in lung cancer bone metastasis. GO and KEGG enrichment analyses suggested that these genes may affect the oxidative stress response, hypoxia response, rough endoplasmic reticulum, mitochondrial outer membrane, iron-sulfur cluster binding, virus receptor activity, central carbon metabolism in cancer, the interleukin-17 (IL-17) signaling pathway, and other aspects to participate in the occurrence and development of lung cancer bone metastasis. Among the 105 lung cancer patients included in the study, 39 cases had bone metastasis, and the incidence rate was 37.14%. A high Eastern Cooperative Oncology Group (ECOG) score and serum ALP and NSE overexpression were associated with bone metastasis in patients with lung cancer. By assessing the risk of bone metastasis in patients with lung cancer, we found that the Area Under Curves (AUCs) of serum ALP and NSE alone and combined were >0.70. Conclusions The differentially expressed ferroptosis-related genes and predicted miRNA regulatory network in lung cancer bone metastasis and the related functional enrichment analysis provide new targets for the treatment of lung cancer bone metastasis. At the same time, from a serological perspective, it was found that early monitoring of serum ALP and NSE expression in patients with lung cancer could be considered to assess the risk of bone metastasis in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis

Zhou,

Xu,

et al. 2023

J Thorac Dis

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“…Li et al found that PEVs from NPC patients induced the metastasis of NPC cells by upregulating ITGB3 expression. Upregulating ITGB3 increased SLC7A11 expression by activating the MAPK/ERK/ATF4/Nrf2 axis and enhancing protein stability, that suppressed ferroptosis, therefore promoting the distant metastasis of NPC cells 42 . Many other studies also shown that PEVs could transfer to target cells and their cargoes promoted phenotypic changes and novel functions of target cells which influenced the progression of tumor 43 .…”

Section: Evs Affect Various Processes Of Npcmentioning

confidence: 96%

The role of extracellular vesicles in the development of nasopharyngeal carcinoma and potential clinical applications

et al. 2023

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Background: Extracellular vesicles (EVs) can be secreted by a wide variety of cells, including tumor cells, and contain some bioactive molecules from the source cells. Therefore, they can potentially be used as biomarkers for early diagnosis of tumors and for tumor therapy. In addition, EVs can affect the features of target cells and participate in regulating the development process of tumors. Methods:A literature review was conducted to elucidate the role of extracellular vesicles in the progression and treatment of nasopharyngeal carcinoma. Results:In this review, we discuss the molecular mechanisms of cell proliferation, angiogenesis, epithelial-mesenchymal transformation and metastasis, immune response, and chemo-radiotherapy resistance that are induced by EVs. We also reviewed the potential applications of EVs as biomarkers, therapeutic agents, and carriers so as to determine new directions for the early diagnosis and targeted therapy of nasopharyngeal carcinoma. The application limitations have also been discussed in this review, further work is needed to ensure optimal outcomes for patients. Conclusion:Although the roles of extracellular vesicles in the progression of nasopharyngeal carcinoma have been summarized, some aspects are still unclear and need to be further studied. In addition, the applications of extracellular vesicles in the treatment of nasopharyngeal carcinoma still need to optimize conditions to produce better therapeutic outcomes for patients with nasopharyngeal carcinoma.

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“…Moreover, other processes such as tumour progression and metastasis can also be affected by non-tumour-derived exosomes [ 194 , 195 , 196 ]. Although there are some novel studies on the effects of exosomes derived from endothelial cells and platelets on metastasis and therapy resistance in NPC, such work is limited [ 197 , 198 ]. In future studies of NPC, it is important to diversify these directions and avoid an excessive focus solely on TEX.…”

Section: Limitations Of Exosomes In Clinical Use and Future Directionsmentioning

confidence: 99%

Unfolding the Complexity of Exosome–Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma

Chak,

Kam,

Choi

et al. 2024

Cancers

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Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30–150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell–cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease.

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Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3

Cited by 24 publications

References 45 publications

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis

Identification of the potential ferroptosis key genes in lung cancer with bone metastasis

The role of extracellular vesicles in the development of nasopharyngeal carcinoma and potential clinical applications

Unfolding the Complexity of Exosome–Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma

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