Inhibition of tumor growth and vasculogenic mimicry by curcumin through down-regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model

Chen, Lu Xia; He, Yan; Zhao, Shengyuan; Wu, Jian; Wang, Jian Tao; Zhu, Li; Lin, Tzu-Shun; Sun, Bei; Li, Xiao Rong

doi:10.4161/cbt.11.2.13842

Cited by 73 publications

(58 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, inhibition of miR-141 led to increased phosphorylation of FAK and AKT. Additional downstream mediators of FAK/AKT such as MMPs (MMP-2/9) that have been implicated in the aggressiveness of RCC (37,38) are known to contribute to FAK/AKTmediated cell proliferation and progression (47)(48)(49)(50), which is further supported by our study on the functional activities of miR-141 and EphA2. However, further investigation of EphA2/p-FAK/p-AKT/MMP pathway regulation in RCC is mandatory.…”

Section: Discussionsupporting

confidence: 71%

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

Chen

Wang

Ruan

et al. 2014

Clinical Cancer Research

124

117

View full text Add to dashboard Cite

Purpose: Although microRNAs (miRNA) have been revealed as crucial modulators of tumorigenesis, our understanding of their roles in renal cell carcinoma (RCC) is limited. Here we sought to identify human miRNAs that act as key regulators of renal carcinogenesis.Experimental Design: We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues.Results: A total of 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an area under the receiver operating characteristics curve of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G 0 -G 1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the antitumor activities of miR-141 were mediated by its reversal regulation of erythropoietin-producing hepatocellular (Eph) A2 (EphA2), which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9.

show abstract

Section: Discussionsupporting

confidence: 71%

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

Chen

Wang

Ruan

et al. 2014

Clinical Cancer Research

124

117

View full text Add to dashboard Cite

show abstract

“…Various molecules involved in VM formation have been investigated in different tumors, including HIF-1α (14,35), VE-cadherin (36,37), EphA2 (37,38), MMP-14 (39), MMP-2 (39) and Ln-5-γ2 chain (40). Following the identification of the above-described molecules involved in VM, a classical model of the signaling cascade implicated in VM was suggested (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α

Min

Sun

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Abstract. The mammalian target of rapamycin (mTOR) is a crucial regulator in malignant gliomas. Vasculogenic mimicry (VM) describes functional channels established by highly malignant tumor cells that is different from endothelium-lined blood vessels. Our previous studies confirmed the existence and clinical significance of VM in medulloblastoma and glioblastoma. In the present study, by immunohistochemical and CD34/PAS histochemical double-staining, 34 cases (26.8%) with VM structures were identified among a total of 127 glioma cases, and these VM structures were associated with mTOR expression in the glioma specimens. In vitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. In addition, rapamycin and mTOR siRNA inhibited molecules in the signaling cascade of VM formation, particularly HIF-1α. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas.

show abstract

“…Angiogenesis describes the process of the formation of novel vessels from the existing vasculature. The identification of non-endothelialized vessel-like channels in malignant tumors, termed VM, has provided insight into underlying tumor behaviors and presents potential targets for drug therapy (10,16). The formation of VM by tumor cells requires a genetic reversion of cells to a pluripotent embryonic-like genotype, a change known as 'cancer plasticity' (6,17,18).…”

Section: Discussionmentioning

confidence: 99%

Vasculogenic mimicry is a major feature and novel predictor of poor prognosis in patients with orbital rhabdomyosarcoma

Chen

Sun

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Vasculogenic mimicry (VM) is a key developmental program, frequently activated during cancer invasion and metastasis. The aim of the present study was to evaluate the role of VM in orbital rhabdomyosarcoma (RMS), the correlation between VM and tumor differentiation, recurrence and survival duration, as well as the contribution of epithelial cell kinase (EphA2) and matrix metalloproteinase-2 (MMP-2) in VM initiation. A total of 32 patients were enrolled to investigate the associations between VM in orbital RMS tumors and clinical characteristics, as well as its impact on overall survival. VM was identified and confirmed by CD31/periodic acid-Schiff double staining, while the presence of EphA2 and MMP-2 were examined by immunohistochemical analysis. VM was identified in eleven patients, particularly those with poorly differentiated orbital RMS (P=0.001). Patients with VM exhibited significantly worse survival rates (P= 0.001, log-rank test), a significantly increased risk of mortality (P=0.008) and EphA2 and MMP-2 expression levels were enhanced (P=0.005 and 0.001, respectively). The VM and mitotic rate were independent predictors of poor prognosis (P=0.001 and 0.004, respectively), indicated by multivariate Cox proportional hazards models. These results demonstrated that VM is present in orbital RMS and represents an independent prognostic factor for overall survival. In addition, overexpression of EphA2 and MMP-2 may promote VM formation in orbital RMS. IntroductionOrbital rhabdomyosarcoma (RMS) as a prevalent malignancy, and is the most common malignant tumor of the orbit amongst children (1,2). Malignant tumors require a sufficient blood supply in order to support their growth. It was previously believed that blood vessels were only able to be formed by endothelial cells. However, the rigid cellular identity of the blood vessel has since been questioned, following the observation that tumor cells are also capable of forming extravascular networks in high-grade malignancies (3). The process of vasculogenic mimicry (VM), describes the mechanism by which highly aggressive tumor cells are able to form vessel-like structures, as a result of their high plasticity. It has therefore been suggested that tumors may develop vascularization via angiogenesis, and that this process is associated with poor prognosis (4-6).Orbital RMS is a solid tumor with the morphological characteristic of bidirectional differentiation, which is the cellular basis of the formation of VM (7). However, to the best of our knowledge, no specific study regarding the novel blood-supplying pattern in orbital RMS has previously been published. Furthermore, the precise molecular mechanism of VM formation remains to be elucidated. Epithelial cell kinase (EphA2) and matrix metalloproteinase-2 (MMP-2) have been found to be a crucial inducers of VM (8,9), therefore it is of significant interest to examine the role of EphA2 and MMP-2 in VM formation in orbital RMS. The present pilot study was designed to investigate whether VM occurs in orbital...

show abstract

Inhibition of tumor growth and vasculogenic mimicry by curcumin through down-regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model

Cited by 73 publications

References 23 publications

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α

Vasculogenic mimicry is a major feature and novel predictor of poor prognosis in patients with orbital rhabdomyosarcoma

Contact Info

Product

Resources

About