Functional significance of VEGF-a in human ovarian carcinoma: Role in vasculogenic mimicry

Wang, Jun Yan; Sun, Tao; Zhao, Xuyao; Zhang, Shi Wu; Zhang, Dan Fang; Gu, Qing; Wang, Xinghui; Zhao, Nan; Qie, Shuo; Sun, Bei

doi:10.4161/cbt.7.5.5765

Cited by 90 publications

(85 citation statements)

References 30 publications

(41 reference statements)

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“…Although several cytokines elicit MMP expression in ovarian carcinoma, VEGF is particularly important because it plays major role in ovarian cancer (50). However, the transcriptional regulation of MMP gene upon VEGF stimulation has not been studied yet.…”

mentioning

confidence: 99%

ETS-1 Protein Regulates Vascular Endothelial Growth Factor-induced Matrix Metalloproteinase-9 and Matrix Metalloproteinase-13 Expression in Human Ovarian Carcinoma Cell Line SKOV-3

Ghosh

Basu

Roy

2012

Journal of Biological Chemistry

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Background:The mechanism of vascular endothelial growth factor (VEGF)-regulated expression of MMPs followed by cancer cell scattering/invasion is poorly understood. Results: VEGF induces MMP-9, MMP-13, and ETS-1 through PI3K/AKT and p38 MAPK pathways in SKOV-3 cells. Conclusion: VEGF induces ETS-1, which activates specific MMPS, leading to the invasion/scattering in SKOV-3 cells. Significance: This study provides useful information that reveals the molecular mechanism of ovarian cancer metastasis.

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mentioning

confidence: 99%

ETS-1 Protein Regulates Vascular Endothelial Growth Factor-induced Matrix Metalloproteinase-9 and Matrix Metalloproteinase-13 Expression in Human Ovarian Carcinoma Cell Line SKOV-3

Ghosh

Basu

Roy

2012

Journal of Biological Chemistry

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“…Abundant expression of VEGF was also confirmed in the VM group of the present study. Findings of other studies also showed that VM was mediated by VEGF-A in other carcinomas, such as melanoma [23] and ovarian cancer [24]. In contrast, others found that VEGF expression was not increased or even decreased in the presence of VM [25].…”

Section: Discussionmentioning

confidence: 80%

Significance of Vasculogenic Mimicry Formation in Gastric Carcinoma

Sun

et al. 2017

Oncol Res Treat

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Background: The purpose of this study was to evaluate the clinical significance and prognostic roles of vasculogenic mimicry (VM) and elucidate their intrinsic association with molecular markers. Methods: 89 human gastric cancer cases with detailed follow-up and clinicopathologic data were collected. CD34/periodic acid-Schiff double staining was performed to validate the existence of VM. Immunohistochemistry was performed to explore the expression of different molecular factors. Results: VM was observed in 24 gastric cancer patients. They were prone to higher histological grade, hematogenous metastasis, distant recurrence, and chance of progression to stage III or IV (p < 0.05). The VM group had shorter overall and disease-free survival (p < 0.05). VM negativity was independently prognostic for prolonged overall or disease-free survival (p < 0.05). VM was positively associated with levels of matrix metalloproteinase-2, matrix metalloproteinase-9, vascular endothelial growth factor, and vascular endothelial growth factor receptor-1 (p < 0.05), but not with vascular endothelial growth factor receptor-2 (p > 0.05). Conclusion: VM should be regarded as a good marker to indicate pathobiological behaviors of gastric cancer. Using antibodies against matrix metalloproteinases, vascular endothelial growth factor, or vascular endothelial growth factor receptors could be strategies to counteract VM formation.

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“…S3C). Autocrine production of VEGF-A has been shown to be a major player in the functional plasticity of aggressive cancer cells forming vascular networks (24,25). Using a tube formation assay, we observed that siTIMP4 cells were not able to form elongated structures (Fig.…”

Section: Timp4 Regulates Cellular Invasion and Migration And Vegf Expmentioning

confidence: 89%

Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers

Boufraqech

Zhang

Nilubol

et al. 2016

Clinical Cancer Research

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Purpose: Epithelial-to-mesenchymal transition (EMT) is important in cancer progression and metastasis. We and others have previously reported that lysyl oxidase (LOX) is overexpressed in aggressive cancers, is associated with increased mortality, and regulates EMT. However, the mechanism by which LOX mediates EMT is unknown. In this study, we investigated the effect of LOX on mediators of EMT.Experimental Design: We used chromatin immunoprecipitation and promoter luciferase assays to determine the target gene of LOX. To determine the effects of SNAI2 in vivo, we used our metastatic anaplastic thyroid cancer (ATC) mouse model. To investigate the effects of LOX and SNAI2 on MMPs and TIMPs, protein arrays were used. Primary tumors from patients with metastatic, breast and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and TIMP4 expression by immunohistochemistry.Results: We found that LOX knockdown decreases SNAI2 expression in cancer cell lines. Furthermore, knockdown of LOX reduced SNAI2 expression in a metastatic mouse model of thyroid cancer. We also demonstrated that LOX binds and transactivates the SNAI2 promoter. We found a direct correlation in thyroid and breast cancer samples between LOX and SNAI2 expression. To understand how LOX/SNAI2 axis mediates these effects, we performed a comprehensive analysis of MMPs/TIMPs. LOX and SNAI2 depletion reduced TIMP4 secretion. Analysis of SNAI2 and TIMP4 expression showed overexpression of both proteins in aggressive thyroid, colon, and breast tumors.Conclusions: Our findings provide new evidence that LOX regulates SNAI2 expression and that SNAI2-mediated TIMP4 secretion plays a role in cancer progression.

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Functional significance of VEGF-a in human ovarian carcinoma: Role in vasculogenic mimicry

Cited by 90 publications

References 30 publications

ETS-1 Protein Regulates Vascular Endothelial Growth Factor-induced Matrix Metalloproteinase-9 and Matrix Metalloproteinase-13 Expression in Human Ovarian Carcinoma Cell Line SKOV-3

ETS-1 Protein Regulates Vascular Endothelial Growth Factor-induced Matrix Metalloproteinase-9 and Matrix Metalloproteinase-13 Expression in Human Ovarian Carcinoma Cell Line SKOV-3

Significance of Vasculogenic Mimicry Formation in Gastric Carcinoma

Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers

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