Phosphatidylserine-exposing tumor-derived microparticles exacerbate coagulation and cancer cell transendothelial migration in triple-negative breast cancer

Zhang, Cong; Zhong, Yang; Zhou, Peng; Yu, Mengxue; Li, Baorong; Liu, Yingmiao; Jin, Jiaqi; Liu, Wenhui; Jing, Haijiao; Du, Jingwen; Hui, Hui; Zhao, Zhiyu; wang, Jianxin; Chu, Yinzhu; Zhang, Chunmei; Novakovic, Valerie A.; Shi, Jialan; Wu, Changjun

doi:10.7150/thno.53637

Cited by 17 publications

(16 citation statements)

References 60 publications

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“…In addition, there are reports that blood cell‐derived mEVs express PS and are related to cancer malignancy, 44 , 45 but there are also reports that tumor‐derived mEVs express PS. 46 In Figure S4 , we observed that some CEACAM+ EVs were positive for annexin V. These might be involved in some cancer characteristics, as described above. 46 …”

Section: Discussionmentioning

confidence: 51%

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Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

et al. 2022

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Early detection and long‐term monitoring are important for urothelial carcinoma of the bladder (UCB). Urine cytology and existing markers have insufficient diagnostic performance. Here, we examined medium‐sized extracellular vesicles (EVs) in urine to identify specific markers for UCB and evaluated their usefulness as diagnostic material. To identify specific markers in urinary EVs derived from UCB, we undertook shotgun proteomics using urine from four UCB patients and four healthy subjects. Next, 29 healthy specimens, 18 noncancer specimens, and 33 UCB specimens, all from men, were analyzed for urinary EVs by flow cytometry to evaluate the diagnostic performance of UCB‐specific EVs. Nanoparticle‐tracking analysis indicated that the size of EVs extracted from urine was mostly <400 nm. By shotgun proteomics, we detected several proteins characteristic of UCB and found that carcinoembryonic antigen‐related adhesion molecule (CEACAM) proteins were increased in patients. Flow cytometric analysis revealed that the degree of expression of CEACAM1, CEACAM5, and CEACAM6 proteins on the surface of EVs varied among patients. Extracellular vesicles expressing CEACAM proteins also expressed mucin 1, suggesting that they were derived from tumorigenic uroepithelial cells. The number of EVs expressing CEACAM1, 5, and 6 proteins was significantly increased in UCB (mean ± SD, 8.6 ± 13%) compared to non‐UCB (0.69 ± 0.46) and healthy (0.46 ± 0.34) by flow cytometry. The results of receiver operating characteristic (ROC) analysis showed a good score of area under the ROC curve of 0.907. We identified EVs that specifically express CEACAM proteins in urine and have potential for diagnostic applications. These EVs are potential targets in a new liquid biopsy test for UCB patients.

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Section: Discussionmentioning

confidence: 51%

“… 46 In Figure S4 , we observed that some CEACAM+ EVs were positive for annexin V. These might be involved in some cancer characteristics, as described above. 46 …”

Section: Discussionmentioning

confidence: 51%

Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

et al. 2022

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“…Moreover, daunorubicin was shown to increase the release of TF+ extracellular vesicles (EV) from THP-1 cells in vitro (Figure 1) (15). Increased anthracycline-induced EV release was confirmed by others (18)(19)(20). DOX-induced EVs are enriched for 4-hydroxy-2-nonenal (4-HNE), a marker for oxidative stress (19).…”

Section: Pro-thrombotic Effects On Vascular Cellsmentioning

confidence: 85%

Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death

Antoniak

Phungphong

Cheng

et al. 2022

Front. Cardiovasc. Med.

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Anthracycline antineoplastic agents such as doxorubicin are widely used and highly effective component of adjuvant chemotherapy for breast cancer and curative regimens for lymphomas, leukemias, and sarcomas. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that typically manifests as cardiomyopathy and can progress to the potentially fatal clinical syndrome of heart failure. Decades of pre-clinical research have explicated the complex and multifaceted mechanisms of anthracycline-induced cardiotoxicity. It is well-established that oxidative stress contributes to the pathobiology and recent work has elucidated important central roles for direct mitochondrial injury and iron overload. Here we focus instead on emerging aspects of anthracycline-induced cardiotoxicity that may have received less attention in other recent reviews: thrombosis, myocardial atrophy, and non-apoptotic programmed cell death.

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“…Tumor-derived EVs participate in organotropic metastasis via pre-metastatic niche construction ( Mo et al, 2021 ). Zhang et al showed that chemotherapy-induced a massive release of phosphatidylserine+ BC cell-derived microparticles (BCMPs), which could be utilized by cancer cells to promote endothelial leakiness and boost metastasis ( Zhang et al, 2021 ). The circulating EVs from BC patients promoted matrix metalloproteinase (MMP)-2 and MMP-9 secretion, migration, and invasion of MDA-MB-231 cells by inducing activation of Src and focal adhesion kinase ( Ramirez-Rícardo et al, 2020 ).…”

Section: Extracellular Vesicles In Triple-negative Breast Cancer Meta...mentioning

confidence: 99%

Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

Dong

Liu

et al. 2022

Front. Cell Dev. Biol.

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Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) with diverse biological behavior, high aggressiveness, and poor prognosis. Extracellular vesicles (EVs) are nano-sized membrane-bound vesicles secreted by nearly all cells, and are involved in physiological and pathological processes. EVs deliver multiple functional cargos into the extracellular space, including proteins, lipids, mRNAs, non-coding RNAs (ncRNAs), and DNA fragments. Emerging evidence confirms that EVs enable pro-oncogenic secretome delivering and trafficking for long-distance cell-to-cell communication in shaping the tumor microenvironment (TME). The transferred tumor-derived EVs modify the capability of invasive behavior and organ-specific metastasis in recipient cells. In addition, TNBC cell-derived EVs have been extensively investigated due to their promising potential as valuable biomarkers for diagnosis, monitoring, and treatment evaluation. Here, the present review will discuss the recent progress of EVs in TNBC growth, metastasis, immune regulation, as well as the potential in TNBC diagnosis and treatment application, hoping to decipher the advantages and challenges of EVs for combating TNBC.

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Phosphatidylserine-exposing tumor-derived microparticles exacerbate coagulation and cancer cell transendothelial migration in triple-negative breast cancer

Cited by 17 publications

References 60 publications

Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death

Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

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