Inhibition of Bevacizumab-induced Epithelial–Mesenchymal Transition by BATF2 Overexpression Involves the Suppression of Wnt/β-Catenin Signaling in Glioblastoma Cells

Huang, Wenqiu; Zhang, Chenguang; Cui, Mengtian; Niu, Jing; Ding, Wei

doi:10.21873/anticanres.11821

Cited by 13 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis is supported by the gradual decrease in replicative activity among cancer cells in the present study, when the TGF-β1 concentration was reduced to 20 and 10 ng/ml. Other studies also support this hypothesis ( 18 , 19 ).…”

Section: Discussionsupporting

confidence: 60%

“…However, as demonstrated in a previous study, cells of this line expressing the epitope prominin-1 (CD133) have high similarity of proteasomal profiles with neural CD133 + human stem cells and significant proteomic differences compared with normal mesenchymal stem cells of the human bone marrow ( 20 ). In a previous study ( 19 ), stimulation of U87 glioblastoma cells with TGF-β1 led to a significant increase in the expression of proteins associated with EMT, which markedly increased their invasiveness. These arguments served as the basis for choosing this line of tumor cells for studying the processes of cell-cell interaction in vitro .…”

Section: Methodsmentioning

confidence: 83%

“…Transforming growth factor (TGF)-β1 serves a key role in EMT-inducing mechanisms. This cytokine has been demonstrated to trigger EMT in certain cases of breast cancer ( 13 ), renal carcinoma ( 14 ), intestinal tumors ( 15 – 17 ), pancreatic cancer ( 18 ) and glioblastoma ( 19 ). Previous research ( 20 ) demonstrated that stimulation of U87 MG cell lines with TGF-β1 significantly increases the production of proteins associated with invasion, proliferation, migration, DNA regeneration, stemness, and resistance to drugs and radiation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

et al. 2018

View full text Add to dashboard Cite

The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial-mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs. Transforming growth factor-β1 (TGF-β1) serves a key role in EMT-inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF-β1 in vitro. The materials for the study were hematopoietic progenitor cell antigen CD34+ hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods, automated monitoring of cell-cell interactions, confocal laser microscopy, flow cytometry and electron microscopy were used. It was demonstrated that U87 cells have a complex communication system, including adhesive intercellular contacts, areas of interdigitation with dissolution of the cytoplasm, cell fusion, communication microtubes and microvesicles. TGF-β1 affected glioblastoma cells by modifying the cell shape and intensifying their exocrine function. HSCs migrated to glioblastoma cells, interacted with them and exchanged fluorescent tags. Stimulation of cancer cells with TGF-β1 weakened the ability of glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to ‘switch’ the proliferation and invasion processes in glioblastoma cells.

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Methodsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

et al. 2018

View full text Add to dashboard Cite

show abstract

“…EMT has been proven to be an important early event of tumor cell metastatic dissemination, in which cells are endowed with a more motile and invasive potential (41, 42). Previously, Huang W et al reported Bevacizumab induced EMT phenotype in glioblastoma cell line U87MG and the overexpression of BATF2 (basic leucine zipper ATF-like transcription factor 2), a multi-target transcriptional repressor, significantly inhibited Bevacizumab-induced EMT with suppression of Wnt/β-catenin signaling (43). In pancreatic cancer, Carbone et al established and validated two murine models of human pancreatic cancer resistant to Bevacizumab in vivo .…”

Section: Discussionmentioning

confidence: 99%

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition

Zhang

Chen

et al. 2019

Front. Immunol.

View full text Add to dashboard Cite

The AURELIA trial demonstrated that adding Bevacizumab to chemotherapy significantly improved progression-free survival (PFS) for platinum resistant recurrent ovarian cancer. Recently, immunotherapy also presented potential anti-tumor effects in several malignant solid tumors. This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing <6 months after completing platinum-based therapy. Based on responding to at least 2 cycles of Bevacizumab-containing chemotherapy (BC), these Patients were divided into BC response group and BC non-response group. Immunohistochemistry was used to detect that PD-L1 expression and tumor angiogenesis-related proteins (VEGF and Semaphorin4D) in tissues from 124 patients with CREOC. The positive expressions of PD-L1, VEGF, and Semaphorin4D (SEMA4D) were found in 58.73, 50.79, and 71.43% of the 63 cases CREOC tissues with BC response, respectively, which were significantly higher than that in the 61 cases BC non-response group ( P < 0.05). PD-L1 expression correlated with SEMA4D and VEGF positively ( r = 0.344 and 0.363, P < 0.001). Over-expressions of PD-L1, VEGF and SEMA4D are associated with more malignant clinicopathologic characteristics of CREOC Patients. In survival analysis, patients' response to BC was the independent factor for evaluation of PFS and overall survival (OS). Cell functional assays showed that Atezolizumab in combination with Bevacizumab inhibited the proliferation, migration, and invasion of cisplatin resistant ovarian cancer cell line A2780cis in vitro synergistically, which maybe associate with Bevacizumab suppressing the epithelial-mesenchymal transition (EMT) and PD-L1 expression by targeting STAT3. Furthermore, Bevacizumab and Atezolizumab induced synergistic anti-tumor effect in vivo . These findings suggest a novel therapeutic strategy for cisplatin resistant recurrent EOC and its mechanism warrants further study.

show abstract

“…However, these therapies exhibit certain disadvantages. For instance, bevacizumab, which is an inhibitor of the biological activity of vascular endothelial growth factor (VEGF) and is widely used in GBM treatment, stimulates EMT ( 56 , 57 ). This drawback is typical for tyrosine kinase inhibitors targeting tumor angiogenesis.…”

Section: Complex Therapy Of Glioblastoma and Csc Protein Targetsmentioning

confidence: 99%

Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review)

et al. 2018

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and ~20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. Resistance of GBM to treatment can be explained by the presence of cancer stem cells (CSCs) among the GBM cell population. At present, there are no effective therapeutic strategies for the elimination of CSCs. The present review examined the nature of human GBM therapeutic resistance and attempted to systematize and put forward novel approaches for a personalized therapy of GBM that not only destroys tumor tissue, but also regulates cellular signaling and the morphogenetic properties of CSCs. The CSCs are considered to be an informationally accessible living system, and the CSC proteome should be used as a target for therapy directed at suppressing clonal selection mechanisms and CSC generation, destroying CSC hierarchy, and disrupting the interaction of CSCs with their microenvironment and extracellular matrix. These objectives can be achieved through the use of biomedical cellular products.

show abstract

Inhibition of Bevacizumab-induced Epithelial–Mesenchymal Transition by BATF2 Overexpression Involves the Suppression of Wnt/β-Catenin Signaling in Glioblastoma Cells

Abstract: Our findings expanded the understanding of the role of BATF2 in tumors, and also suggested a potential of using BATF2 as a therapeutic target to hinder bevacizumab induced EMT in glioblastoma.

Cited by 13 publications

References 39 publications

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in�vitro

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition

Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review)

Contact Info

Product

Resources

About