CCR7 Mediates TGF-β1-Induced Human Malignant Glioma Invasion, Migration, and Epithelial–Mesenchymal Transition by Activating MMP2/9 Through the Nuclear Factor KappaB Signaling Pathway

Zheng, Yanyan; Miu, Yiting; Yang, Xiaokai; Yang, Xiao-Guo; Zhu, Mei-Jia

doi:10.1089/dna.2017.3818

Cited by 24 publications

(16 citation statements)

References 39 publications

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“…A few studies suggest that P188 might inhibit the NF-kB signaling pathway 41 . If validated, it would provide a clearer understanding of the interaction between P188 and NF-kB that is a known transcription factor for MMP expressions 33,42,43 . In an animal model study, Wang et al 39 demonstrated that P188 exerts neuroprotective effects by preventing MMP-mediated tight junction degradation.…”

Section: Discussionmentioning

confidence: 99%

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Inyang

Abhyankar

Chen

et al. 2020

Sci Rep

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Brain injuries caused by an explosive blast or blunt force is typically presumed to associate with mechanical trauma to the brain tissue. Recent findings from our laboratory suggest that shockwaves produced by a blast can generate micron-sized bubbles in the tissue. the collapse of microbubbles (i.e., microcavitation) may induce a mechanical trauma and compromise the integrity of the blood-brain endothelium (BBE). To test our hypothesis, we engineered a BBE model to determine the effect of microbubbles on the structural and functional changes in the BBe. Using monolayers of mouse primary brain microvascular endothelial cells, the permeability coefficient was measured following simulated blast-induced microcavitation. this event down-regulated the expression of tight junction markers, disorganized the cell-cell junction, and increased permeability. Since poloxamers have been shown to rescue damaged cells, the cells were treated with the FDA-approved poloxamer 188 (P188). The results indicate P188 recovered the permeability, restored the tight junctions, and suppressed the expressions of matrix metalloproteinases. the biomimetic interface we developed appears to provide a systematic approach to replicate the structure and function of BBe, determine its alteration in response to traumatic brain injury, and test potential therapeutic treatments to repair the damaged brain endothelium. Traumatic brain injury (TBI) is one of the major causes of emergency visits and hospitalization. In 2010, the Centers for Disease Control reported about 2.5 million emergency department visits, hospitalizations, and deaths here in the United States alone 1. TBIs are also caused by an explosive blast or blunt force to the head especially among those who serve in the U.S. military 2-4. The trauma can lead to endothelial cell detachment, tight junction disruption, and altered blood-brain barrier (BBB) permeability 5,6. One of the unique features of BBB is the regulation of biotransport through a monolayer of brain endothelial cells (BECs). BECs are highly regulated in their structure and function by the tight junction complex that is composed of, among many molecules, zonula occludens (ZO-1) and the occludins family 7,8. Only particles with a molecular mass of less than 500 Daltons can cross the BBB efficiently 9. However, the structural integrity of the BBB can be mechanically and biochemically compromised 10-13 , allowing harmful substances to extravasate into the brain. The leaky brain endothelium, in turn, may lead to secondary brain injury 14-16. Several sophisticated TBI models of explosive blast or blunt force have been studied. However, the potential mechanisms connecting shock wave exposure to the head and to TBI are still not well understood 17. One of the mechanical traumas that have been investigated in our laboratory is the formation of micron-size bubbles in response to shock wave and subsequent collapse of such microbubbles, referred to as microcavitation 18. The collapse of highly pressurized microbubbles is thought to prod...

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Section: Discussionmentioning

confidence: 99%

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Inyang

Abhyankar

Chen

et al. 2020

Sci Rep

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“…CXCR4 silencing could suppress the invasion and adhesion potential of U87 cells and pancreatic cancer cells, and decrease the transcriptional activity of NF-κB promoter (43,52). CCR7 could activate MMP2 and MMP9 through the NF-κB signaling pathway to mediate the migration and invasion of human malignant glioma, and these biological effects could be reversed by treatment with small interfering CCR7 or a CCR7 neutralizing antibody in vitro (93). In another PNI tumor, CCA, studies showed that NF-κB signaling could be activated by the CCL5/CCR5 axis through increasing the expression of MMP2 and MMP9, thus contributing to the invasion and metastasis of tumor cells, which could be inhibited by CCL5 neutralizing antibody or CCR5 inhibitor maraviroc (94).…”

Section: Reciprocal Interaction Between Other Factors and Chemokines mentioning

confidence: 99%

Functions of chemokines in the perineural invasion of tumors (Review)

et al. 2018

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The perineural invasion (PNI) of malignant tumors is a form of tumor progression in which cancer cells encroach along nerves. PNI hinders curative resection. Residual tumor cells in or around nerves can bring about local recurrence, infiltration and metastasis. This behavior is usually associated with a poor clinical prognosis. Therefore, it is necessary to investigate novel ligand-receptor crosstalk between nerves and tumor cells that promote the process of PNI. Chemokines are regarded as one of pivotal factors involved in the process of PNI. The present review collates information provided by previous studies with regard to the role of chemokines in PNI. The study presents a definition of PNI in cancer, generalizes the biological characteristics and the expression of chemokines and their receptors in cancer types associated with PNI, and discusses the underlying molecular mechanisms of chemokines, the reciprocal interactions between chemokines and other factors in PNI, and the interconnectivity of the microenvironment and chemokines. The aim of the review is to thoroughly illustrate the molecular cues of chemokines in cancer with PNI and to identify novel antitumor targets.

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“…TGF-β is a master regulator of mesenchymal transition in GBM and induces the expression of mesenchymal genes, such as N-cadherin, ZEB1, Slug and CD44 [ 17 , 36 , 37 ]. Moreover, GSEA results showed that GBMs with high-level of PBX3 were enriched for the TGF-β signaling (Additional file 3 : Figure S3).…”

Section: Resultsmentioning

confidence: 99%

PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion

Bao

Liu

et al. 2018

J Exp Clin Cancer Res

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BackgroundBrain invasion by glioblastoma (GBM) determines recurrence and prognosis in patients, which is, in part, attributed to increased mesenchymal transition. Here, we report evidence favoring such a role for the Pre-B-cell leukemia homebox (PBX) family member PBX3.MethodsWestern blot, immunohistochemistry, qRT-PCR and datasets mining were used to determined proteins or genes expression levels. Wound-healing and transwell assays were used to examine the invasive abilities of GBM cells. Dual-luciferase reporter assays were used to determine how let-7b regulates PBX3. Chromatin-immunoprecipitation (ChIP) and rescue experiments were performed to investigate the involved molecular mechanisms. Orthotopic mouse models were used to assess the role of PBX3 in vivo.ResultsWe found that PBX3 expression levels positively correlated with glioma mesenchymal markers. Ectopic expression of PBX3 promoted invasive phenotypes and triggered the expression of mesenchymal markers, whereas depletion of PBX3 reduced GBM cell invasive abilities and decreased the expression of mesenchymal markers. In addition, inhibition of PBX3 attenuated transforming growth factor-β (TGFβ)-induced GBM mesenchymal transition. Mechanistic studies revealed that PBX3 mediated GBM mesenchymal transition through activation of MEK/ERK1/2, leading to increased expression of LIN28 by c-myc. Increased LIN28 inhibited let-7b biogenesis, which then promoted the pro-invasive genes, such as HMGA2 and IL-6. Furthermore, let-7b suppressed PBX3 by directly targeting 3′-UTR of PBX3. Thus, repressed let-7b by PBX3 amplifies PBX3 signaling and forms a positive feedback loop to promote GBM mesenchymal transition.ConclusionsThese data highlight the importance of PBX3 as a key driver of mesenchymal transition and potential therapeutic target.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0841-0) contains supplementary material, which is available to authorized users.

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CCR7 Mediates TGF-β1-Induced Human Malignant Glioma Invasion, Migration, and Epithelial–Mesenchymal Transition by Activating MMP2/9 Through the Nuclear Factor KappaB Signaling Pathway

Cited by 24 publications

References 39 publications

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Modulation of in vitro Brain Endothelium by Mechanical Trauma: Structural and Functional Restoration by Poloxamer 188

Functions of chemokines in the perineural invasion of tumors (Review)

PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion

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