Oncolytic Herpes Virus Armed with Vasculostatin in Combination with Bevacizumab Abrogates Glioma Invasion via the CCN1 and AKT Signaling Pathways

Published on Sep 25, 2019in Molecular Cancer Therapeutics5.615
· DOI :10.1158/1535-7163.MCT-18-0799
Yusuke Tomita6
Estimated H-index: 6
(Okayama University),
Kazuhiko Kurozumi23
Estimated H-index: 23
(Okayama University)
+ 10 AuthorsIsao Date58
Estimated H-index: 58
(Okayama University)
Sources
Abstract
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 assessed by cytotoxicity, migration, and invasion assays. For in vivo experiments, glioma cells were stereotactically inoculated into the brain of mice. RAMBO was intratumorally injected seven days after tumor inoculation, and bevacizumab was administered intraperitoneally twice a week. RAMBO significantly decreased both the migration and invasion of glioma cells treated with bevacizumab. In mice treated with bevacizumab and RAMBO combination, the survival time was significantly longer and the depth of tumor invasion was significantly smaller than those treated with monotherapy of bevacizumab. Interestingly, RAMBO decreased the expression of cysteine-rich protein 61 and phosphorylation of AKT, which were increased by bevacizumab. These results suggest that RAMBO suppresses bevacizumab-induced glioma invasion, which could be a promising approach to glioma therapy.
📖 Papers frequently viewed together
6 Citations
37 Citations
7 Authors (Yuji Piao, ..., John de Groot)
38 Citations
References51
Newest
#1Toshihiko Shimizu (Okayama University)H-Index: 7
#2Joji Ishida (Okayama University)H-Index: 10
Last. Isao Date (Okayama University)H-Index: 58
view all 11 authors...
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 U87ΔE...
6 CitationsSource
#1Yoshihiro Otani (Okayama University)H-Index: 7
#2Tomotsugu Ichikawa (Okayama University)H-Index: 22
Last. Isao Date (Okayama University)H-Index: 58
view all 13 authors...
Fibroblast growth factor 13 regulates glioma cell invasion and is important for bevacizumab-induced glioma invasion
17 CitationsSource
#1Hao-Wen Sim (Princess Margaret Cancer Centre)H-Index: 10
#2Erin R Morgan (Princess Margaret Cancer Centre)H-Index: 1
Last. Warren P. Mason (Princess Margaret Cancer Centre)H-Index: 53
view all 3 authors...
: High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been inves...
16 CitationsSource
#1Arman Jahangiri (UCSF: University of California, San Francisco)H-Index: 24
#2Alan Nguyen (UCSF: University of California, San Francisco)H-Index: 3
Last. Manish K. Aghi (UCSF: University of California, San Francisco)H-Index: 58
view all 20 authors...
The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive resistance to antiangiogenic VEGF neutralizing antibody, bevacizumab. Inducing c-Met/β1 complex formation through an engin...
41 CitationsSource
#1Anna C. Filley (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 5
#2Mario Henriquez (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 4
Last. Mahua Dey (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 22
view all 3 authors...
// Anna C. Filley 1 , Mario Henriquez 1 and Mahua Dey 1 1 Department of Neurosurgery, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, USA Correspondence to: Mahua Dey, email: mdey@iu.edu Keywords: gliolastoma, checkpoint inhibitor, PD-1/PD-L1, malignant glioma, immunotherapy Received: July 13, 2017 Accepted: September 08, 2017 Published: October 06, 2017 ABSTRACT Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in adults. With a median patient ...
191 CitationsSource
#1Yoshihiro Otani (Okayama University)H-Index: 7
#2Joji Ishida (Okayama University)H-Index: 10
Last. Isao Date (Okayama University)H-Index: 58
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...
6 CitationsSource
#1Ibrahim Ragab Eissa (Tanta University)H-Index: 3
#2Yoshinori Naoe (Nagoya University)H-Index: 15
Last. Hideki Kasuya (Nagoya University)H-Index: 26
view all 14 authors...
Oncolytic viruses are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of anti-tumor immune responses. HF10 is an oncolytic herpes simplex virus-1 (HSV-1) with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame shift mutations, in contrast to the majority of engineered oncolytic viruses. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL...
40 CitationsSource
#1Tetsuo Oka (Okayama University)H-Index: 9
#2Kazuhiko Kurozumi (Okayama University)H-Index: 23
Last. Isao DateH-Index: 58
view all 13 authors...
A super gene expression system enhances the anti-glioma effects of adenovirus-mediated REIC/Dkk-3 gene therapy
7 CitationsSource
#1Sang Hoon Han (Jeju National University)H-Index: 7
#2Ngoc Thuy Bui (Jeju National University)H-Index: 3
Last. Dong Bok Shin (Gachon University)H-Index: 26
view all 6 authors...
One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for...
21 CitationsSource
#1Ivy Paw (Wake Forest University)H-Index: 5
#2Richard L. Carpenter (Wake Forest University)H-Index: 22
Last. Hui-Wen Lo (Wake Forest University)H-Index: 36
view all 5 authors...
Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete r...
182 CitationsSource
Cited By10
Newest
#1Mitra Nair (University of Texas at Austin)H-Index: 2
#2Chelsea Bolyard (The Ohio State University Wexner Medical Center)H-Index: 12
Last. Ji Young Yoo (University of Texas Health Science Center at Houston)H-Index: 28
view all 5 authors...
Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1) is an adhesion G protein-coupled receptor that has been found to play key roles in phagocytosis, inflammation, synaptogenesis, the inhibition of angiogenesis, and myoblast fusion. As the name suggests, it is primarily expressed in the brain, with a high expression in the normal adult and developing brain. Additionally, its expression is reduced in brain cancers, such as glioblastoma (GBM) and peripheral cancers, suggesting that BAI1 is a tumo...
Source
#1Omeed Moaven (Mayo Clinic)H-Index: 19
#2Christopher W. Mangieri (Wake Forest University)H-Index: 4
Last. Mitesh J. Borad (Mayo Clinic)H-Index: 43
view all 5 authors...
Despite advancements in cancer therapy that have occurred over the past several decades, successful treatment of advanced malignancies remains elusive. Substantial resources and significant efforts...
Source
#1Hong-My Nguyen (TTUHSC: Texas Tech University Health Sciences Center)H-Index: 2
#2Dipongkor Saha (TTUHSC: Texas Tech University Health Sciences Center)H-Index: 16
Glioblastoma (GBM) is a lethal primary malignant brain tumor with no current effective treatments. The recent emergence of immuno-virotherapy and FDA approval of T-VEC have generated a great expectation towards oncolytic herpes simplex viruses (oHSVs) as a promising treatment option for GBM. Since the generation and testing of the first genetically engineered oHSV in glioma in the early 1990s, oHSV-based therapies have shown a long way of great progress in terms of anti-GBM efficacy and safety, ...
2 CitationsSource
#1Omeed Moaven (Mayo Clinic)H-Index: 19
#2Christopher W. Mangieri (Wake Forest University)H-Index: 4
Last. Mitesh J. Borad (Mayo Clinic)H-Index: 43
view all 5 authors...
Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has s...
Source
#1Atsuhito Uneda (Okayama University)H-Index: 8
#2Kazuhiko Kurozumi (Okayama University)H-Index: 23
Last. Isao Date (Okayama University)H-Index: 58
view all 15 authors...
Glioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment....
4 CitationsSource
#1Dileep D. Monie (Mayo Clinic)H-Index: 6
#2Archis R. Bhandarkar (Mayo Clinic)H-Index: 1
Last. Hu Li (Mayo Clinic)H-Index: 28
view all 7 authors...
Oncolytic viruses (OVs) are a class of immunotherapeutic agents with promising preclinical results for the treatment of glioblastoma (GBM) but have shown limited success in recent clinical trials. Advanced bioengineering principles from disciplines such as synthetic and systems biology are needed to overcome the current challenges faced in developing effective OV-based immunotherapies for GBMs, including off-target effects and poor clinical responses. Synthetic biology is an emerging field that ...
1 CitationsSource
Aberrant vascular network is a hallmark of cancer. However, the role of vascular endothelial cells (VECs)-expressing PD-L1 in tumor immune microenvironment and antiangiogenic therapy remains unclear. In this study, we used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1+ CD34+ VECs and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8+ T cells and FoxP3...
15 CitationsSource
#1Mitra Nair (University of Texas Health Science Center at Houston)H-Index: 2
#2Maninder Khosla (The Ohio State University Wexner Medical Center)H-Index: 1
Last. Ji Young Yoo (University of Texas Health Science Center at Houston)H-Index: 28
view all 16 authors...
Vascularization is a common pathology for many solid tumors, and therefore anti-angiogenic strategies are being investigated as a therapeutic target for treatment. Numerous studies are also being conducted regarding the effects of oncolytic viruses, including ImlygicTM, an FDA approved oncolytic herpes simplex virus-1 (oHSV) for the treatment of highly vascularized tumors such as Kaposi sarcoma (NCT04065152), and brain tumors. To our knowledge, the effects of combining oncolytic HSV with angioge...
2 CitationsSource
#1Yuji Matsumoto (Okayama University)H-Index: 6
#2Tomotsugu Ichikawa (Okayama University)H-Index: 22
Last. Isao Date (Okayama University)H-Index: 58
view all 13 authors...
Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clusterin...
4 CitationsSource
Abstract For patients with advanced hematological malignancies the therapeutic landscape has been transformed by the emergence of adoptive cell transfer utilizing autologous chimeric antigen receptor (CAR)-redirected T-cells. However, solid tumors have proved far more resistant to this approach. Here, we summarize the numerous challenges faced by CAR T-cells designed to target solid tumors, highlighting, in particular, issues related to impaired trafficking, expansion, and persistence. In parall...
7 CitationsSource