δ-Catenin Promotes Bevacizumab-Induced Glioma Invasion.

Published on Apr 1, 2019in Molecular Cancer Therapeutics6.261
· DOI :10.1158/1535-7163.MCT-18-0138
Toshihiko Shimizu6
Estimated H-index: 6
(Okayama University),
Joji Ishida10
Estimated H-index: 10
(Okayama University)
+ 8 AuthorsIsao Date62
Estimated H-index: 62
(Okayama University)
Sources
Abstract
The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed patients with glioblastoma, and this emphasizes the potential of bevacizumab as a glioma treatment. However, although bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting these cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis revealed upregulation of δ-catenin (CTNND2) and several other factors. In vitro, bevacizumab treatment upregulated δ-catenin expression. A low concentration of bevacizumab was not cytotoxic, but tumor cell motility was increased in scratch wound assays and two-chamber assays. Overexpression of δ-catenin increased the tumor invasion in vitro and in vivo. However, δ-catenin knockdown decreased glioma cell invasiveness. The depth of tumor invasion in the U87ΔEGFR cells expressing δ-catenin was significantly increased compared with empty vector-transfected cells. The increase in invasive capacity induced by bevacizumab therapy was associated with upregulation of δ-catenin expression in invasive tumor cells. This finding suggests that δ-catenin is related to tumor invasion and migration.
📖 Papers frequently viewed together
7 Authors (Yuji Piao, ..., John de Groot)
References46
Newest
#1Yoshihiro Otani (Okayama University)H-Index: 8
#2Joji Ishida (Okayama University)H-Index: 10
Last. Isao Date (Okayama University)H-Index: 62
view all 14 authors...
Despite therapeutic advances, glioblastoma represents a lethal brain tumor. Recently, research to identify prognostic markers for glioblastoma has intensified. Our previous study demonstrated that median progression-free survival (PFS) and overall survival (OS) of patients with high cysteine-rich protein 61 (CCN1) expression was significantly shorter than that of patients with low CCN1 expression. To understand the molecular mechanisms that regulate CCN1 expression, we examined 147 tumour sample...
Source
#1Mehdi Touat (University of Paris)H-Index: 19
#2Ahmed Idbaih (University of Paris)H-Index: 68
Last. Keith L. Ligon (Brigham and Women's Hospital)H-Index: 96
view all 4 authors...
ABSTRACT Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches ...
Source
#1Toshihiko Shimizu (Okayama University)H-Index: 6
#2Kazuhiko Kurozumi (Okayama University)H-Index: 24
Last. Isao Date (Okayama University)H-Index: 62
view all 5 authors...
The formation of tumor vasculature and cell invasion along white matter tracts have pivotal roles in the development and progression of glioma. A better understanding of the mechanisms of angiogenesis and invasion in glioma will aid the development of novel therapeutic strategies. The processes of angiogenesis and invasion cause the production of an array of adhesion molecules and extracellular matrix (ECM) components. This review focuses on the role of adhesion molecules and the ECM in malignan...
Source
#1Joji Ishida (Okayama University)H-Index: 10
#2Kazuhiko Kurozumi (Okayama University)H-Index: 24
Last. Isao Date (Okayama University)H-Index: 62
view all 10 authors...
Recently, research efforts in identifying prognostic molecular biomarkers for malignant glioma have intensified. Cysteine-rich protein 61 (CCN1) is one of the CCN family of matricellular proteins that promotes cell growth and angiogenesis in cancers through its interaction with several integrins. In this study, we investigated the relationships among CCN1, O6-methylguanine-DNA methyltransferase expression, the tumor removal rate, and prognosis in 46 glioblastoma patients treated at the Okayama U...
Source
#1Emily Hamburg-Shields (Case Western Reserve University)H-Index: 3
#2Gregg DiNuoscio (Case Western Reserve University)H-Index: 5
Last. Radhika P. Atit (Case Western Reserve University)H-Index: 21
view all 5 authors...
Fibrosis is an end-stage response to tissue injury that is associated with loss of organ function as a result of excess extracellular matrix (ECM) production by fibroblasts. In skin, pathological fibrosis is evident during keloid scar formation, systemic sclerosis (SSc) and morphea. Dermal fibroblasts in these fibrotic diseases exhibit increased Wnt/β-catenin signalling, a pathway that is sufficient to cause fibrosis in mice. However, in the context of this complex pathology, the precise pro-fib...
Source
#4Kentaro Fujii (Okayama University)H-Index: 10
Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma
Source
#1Emily Hamburg-Shields (Case Western Reserve University)H-Index: 3
#1Thomas Simon (University of Rouen)H-Index: 8
#2Bérénice Coquerel (University of Rouen)H-Index: 5
Last. Jean-Pierre Vannier (University of Rouen)H-Index: 30
view all 8 authors...
Bevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can ...
Source
#1Joji Ishida (Okayama University)H-Index: 10
#2Manabu Onishi (Okayama University)H-Index: 12
Last. Isao Date (Okayama University)H-Index: 62
view all 8 authors...
Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain ...
Source
#1Hui Li (PRC: China Medical University (PRC))H-Index: 11
#2Yi Zhang (PRC: China Medical University (PRC))H-Index: 15
Last. Ping He (PRC: China Medical University (PRC))H-Index: 15
view all 6 authors...
Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human prostate cancer have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human prostate cancer tissues and found that Rsf-1 was overexpressed in 45 % of prostate cancer specimens. There was a significant association between Rsf-1 overexpression and tumor st...
Source
Cited By6
Newest
#1Domenico RibattiH-Index: 113
Last. Francesco PezzellaH-Index: 64
view all 3 authors...
Resistance to anti-vascular endothelial growth factor (VEGF) molecules causes lack of response and disease recurrence. Acquired resistance develops as a result of genetic/epigenetic changes conferring to the cancer cells a drug resistant phenotype. In addition to tumor cells, tumor endothelial cells also undergo epigenetic modifications involved in resistance to anti-angiogenic therapies. The association of multiple anti-angiogenic molecules or a combination of anti-angiogenic drugs with other t...
Source
#1Yasuhiko HattoriH-Index: 7
Last. Yosuke ShimazuH-Index: 6
view all 13 authors...
Source
#1Kate Connor (RCSI: Royal College of Surgeons in Ireland)H-Index: 6
#2David Murray (RCSI: Royal College of Surgeons in Ireland)H-Index: 24
Last. Annette T. Byrne (RCSI: Royal College of Surgeons in Ireland)H-Index: 25
view all 16 authors...
Glioblastoma (GBM), a highly invasive and vascular malignancy is shown to rapidly develop resistance and evolve to a more invasive phenotype following bevacizumab (Bev) therapy. Rho Guanine Nucleotide Exchange Factor proteins (RhoGEFs) are mediators of key components in Bev resistance pathways, GBM and Bev-induced invasion. To identify GEFs with enhanced mRNA expression in the leading edge of GBM tumours, a cohort of GEFs was assessed using a clinical dataset. The GEF βPix/COOL-1 was identified,...
Source
#1Pei Wei (Zunyi Medical College)
Last. Zhiyong Wang (Zunyi Medical College)
view all 5 authors...
Abstract Previous studies suggest that upregulated basic fibroblast growth factor (bFGF) plays a key role in the resistance to anti-vascular endothelial growth factor (VEGF) therapy in glioma. This study reported that anti-VEGF treatment regulated bFGF secretion in a double-edged manner. That is, moderate VEGF neutralization reduced bFGF production, whereas VEGF overblocking enhanced bFGF secretion in glioma cells. Our data provide a new perspective on the treatment of glioma with anti-VEGF, and...
Source
#1Giovanni Luca Gravina (University of L'Aquila)H-Index: 44
#2Andrea Mancini (University of L'Aquila)H-Index: 18
Last. Claudio FestucciaH-Index: 43
view all 13 authors...
Background. Glioblastoma multiforme (GBM) is a devastating disease showing a very poor prognosis. New therapeutic approaches are needed to improve survival and quality of life. GBM is a highly vascularized tumor and as such, chemotherapy and anti-angiogenic drugs have been combined for treatment. However, as treatment-induced resistance often develops, our goal was to identify and treat pathways involved in resistance to treatment to optimize the treatment strategies. Anti-angiogenetic compounds...
Source
#1Xue Yang (Xi'an Jiaotong University)H-Index: 3
#2Bowen Yao (Xi'an Jiaotong University)H-Index: 23
Last. Demao Yao (Xi'an Jiaotong University)H-Index: 1
view all 8 authors...
Abstract Long noncoding RNAs (lncRNAs) exert crucial roles in hepatocellular carcinoma (HCC) progression. LncRNA EIF3J-AS1 is recently reported to be highly expressed in HCC and correlates with recurrence-free survival. However, the biological function of EIF3J-AS1 and its underlying molecular mechanism are unexplored yet. In the current study, we demonstrated that EIF3J-AS1 expression was obviously upregulated in HCC tissues compared to adjacent noncancerous tissues. Moreover, the elevated leve...
Source
#1Yusuke Tomita (Okayama University)H-Index: 7
#2Kazuhiko Kurozumi (Okayama University)H-Index: 24
Last. Isao Date (Okayama University)H-Index: 62
view all 13 authors...
Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in glioblastoma patients. However, bevacizumab has also been reported to induce invasiveness of glioma. In this study, we examined the effects of Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), an oncolytic herpes simplex virus-1 expressing vasculostatin, on bevacizumab-induced glioma invasion. The effect of the combination of RAMBO and bevacizumab in vitro was as...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.