Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer

Zhang, Shibo; Xie, Bingfan; Wang, Lijie; Yang, Hua; Zhang, Haopei; Chen, Yuming; Wang, Feng; Liu, Changqing; He, Huanhuan

doi:10.1172/jci140315

Cited by 45 publications

(32 citation statements)

References 39 publications

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“…Owing to the absence of early symptoms, HOC is usually diagnosed at advanced stages that are difficult to cure by simple surgical resection, and relapse commonly occurs during the clinical course of HOC ( 2 ). Most patients with HOC exhibit peritoneal metastases and suffer from perennial malignant ascites leading to advanced stages, a massive progression and poor prognosis of HOC ( 3 , 4 ). Despite surgical interventions and the administration of anticancer drug combinations, the 5-year survival rate of patients with advanced-stage HOC remains low ( 5 ); owing to the distinct biology of HOC, the effective treatment for this disease remains limited ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‑targeted microbubble destruction‑mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer

2021

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Ultrasound-targeted microbubble destruction (UTMD) has recently been developed as a promising noninvasive tool for organ-and tissue-specific gene or drug delivery. The aim of the present study was to explore the role of UTMD-mediated Sirtuin 3 (SIRT3) overexpression in the malignant behaviors of human ovarian cancer (HOC) cells. Reverse transcription-quantitative PCR was performed to detect SIRT3 mRNA expression levels in normal human ovarian epithelial cells and HOC cell lines; low SIRT3 expression was found in HOC cell lines, and the SKOV3 cell line was used in the following experiments. The SIRT3-microbubble (MB) was prepared, and the effects of ultrasound-treated SIRT3-MB on biological processes of SKOV3 cells were determined. The proliferation, migration, invasion and apoptosis of SKOV3 cells were measured after SIRT3 upregulation by UTMD. Xenograft tumors in nude mice were induced to observe tumor growth in vivo. Upregulation of SIRT3 inhibited the malignant behaviors of SKOV3 cells, whereas UTMD-mediated SIRT3 upregulation further inhibited proliferation, epithelial-mesenchymal transition, invasion and migration, and induced apoptosis of SKOV3 cells, and it also inhibited tumor formation and growth in vivo. Moreover, the present study identified hypoxia inducible factor-1α (HIF-1α) as a target of SIRT3. The present study provided evidence that UTMD-mediated overexpression of SIRT3 may suppress HOC progression through the inhibition of HIF-1α.

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Section: Introductionmentioning

confidence: 99%

Ultrasound‑targeted microbubble destruction‑mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer

2021

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“…(a) promote monocyte transendothelial migration and increase endothelial permeability (Adam et al, 2010;Liu et al, 2018;Zhang et al, 2021). Our group previously confirmed that the α2,6 sialylation of VE-cadherin was decreased in EA.hy926 cells during monocyteendothelial cell interaction (Deng et al, 2017).…”

Section: Discussionmentioning

confidence: 63%

VE‐cadherin N‐glycosylation modified by N‐acetylglucosaminyltransferase V regulates VE‐cadherin–β‐catenin interaction and monocyte adhesion

Zhang

et al. 2021

Experimental Physiology

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Monocyte adhesion is a crucial step in the initial stage of atherosclerosis, and dysfunction of VE-cadherin has been reported to be involved in this process. Our group previously found that VE-cadherin and its binding protein, β-catenin, were modified by sialylation, and the levels of sialylation were decreased in pro-inflammatory cytokinetreated human umbilical vein EA.hy926 cells. In this study, we confirmed that the sugar chains of VE-cadherin were modified by N-acetylglucosaminyltransferase V (GnT-V).We showed that the levels of GnT-V and β1,6-N-acetylglucosamine on the VE-cadherin were reduced in the presence of interleukin-1β, whereas the level of monocyte transendothelial migration was increased. Moreover, the interaction between VE-cadherin and β-catenin was increased, accompanied by an increased accumulation of degradative VE-cadherin and cytoplasmic β-catenin, indicating impairment of cell-cell junctions after interleukin-1β treatment. Furthermore, GnT-V short hairpin RNA and overexpression analysis confirmed that glycosylation of VE-cadherin was modified by GnT-V in EA.hy926 cells, which contributed to the monocyte-endothelial adhesion process. Taken together, these results suggest that the function of VE-cadherin in facilitating monocyte adhesion might result from the decreasing GnT-V expression and disorder of GnT-V-catalysed N-glycosylation.Our study clarified the molecular mechanism of VE-cadherin in regulation of the monocyte adhesion process and provided new insights into the post-transcriptional modifications of VE-cadherin.

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“…Several genes have been confirmed to be closely related to the occurrence and progression of ovarian cancer, including SNAI2 [ 16 ], VCAM1 [ 17 ], BRCA1 [ 18 ], MMP2 [ 19 ], MECOM [ 20 ], MXS1 [ 21 ], PARP1 [ 22 ] and so on. We further analyzed the association between UCP1 and these gene expression.…”

Section: Resultsmentioning

confidence: 99%

UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients

et al. 2022

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Background The uncoupling proteins (UCPs) are critical genes associated with tumorigenesis and chemoresistance. However, little is known about the molecular mechanism of the UCPs in ovarian cancer (OV). Material and methods UCPs expression analysis was conducted using Gene Expression Profiling Interactive Analysis (GEPIA), and its potential in clinical prognosis was analyzed using Kaplan- Meier analyses. The influence of UCPs on immune infiltration was analyzed by TIMER. In addition, the correlation between UCPs expression and molecular mechanisms was investigated by TIMER and Cancer Single-cell State Atlas (CancerSEA). Results UCP1, UCP2, UCP3 and UCP5 expression levels correlated with a favorable prognosis and tumor progression. Moreover, UCP1 expression correlated to several immune cell markers and regulated tumorigenesis, such as tumor invasion, EMT, metastasis and DNA repair. In addition, UCP1 potentially involved in genes expression of SNAI2, MMP2, BRCA1 and PARP1. Conclusions These results implied a critical role of UCP1 in the prognosis and immune infiltration of ovarian cancer. In addition, UCP1 expression participated in regulating multiple oncogenes and tumorigenesis.

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Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer

Cited by 45 publications

References 39 publications

Ultrasound‑targeted microbubble destruction‑mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer

Ultrasound‑targeted microbubble destruction‑mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer

VE‐cadherin N‐glycosylation modified by N‐acetylglucosaminyltransferase V regulates VE‐cadherin–β‐catenin interaction and monocyte adhesion

UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients

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