Cell growth inhibition and apoptosis in breast cancer cells induced by anti-FZD7 scFvs: involvement of bioinformatics-based design of novel epitopes

Zarei, Neda; Fazeli, Mehdi; Mohammadi, Mozafar; Nejatollahi, Foroogh

doi:10.1007/s10549-017-4641-6

Cited by 14 publications

(5 citation statements)

References 35 publications

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“…Functionally, the scFvs inhibited cell growth by inducing cell apoptosis in a TNBC cell line, MDA-MB-231. The reasons why scFvs antibodies are potential therapeutic agents include small size, high affinity, human origin, and specificity [ 89 , 90 ].…”

Section: Therapeutic Potential Of Fzd Receptorsmentioning

confidence: 99%

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Zeng

Chen

2018

IJMS

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Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

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Section: Therapeutic Potential Of Fzd Receptorsmentioning

confidence: 99%

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Zeng

Chen

2018

IJMS

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“…Specific antibodies against CD90, a cancer stem cell marker, were selected by panning using the phage display technology (33). Selection of specific scFv antibodies against Frizzled receptor 7 (FZD7) by panning procedure have shown high inhibitory effects of the scFvs on breast cancer cell growth (34).…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative Effect of Specific Anti-EGFR Single Chain Antibody on Triple Negative Breast Cancer Cells

Abdollahzadeh

Nejatollahi

2020

rbmb.net

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Background: Targeted therapy is an important treatment strategy that is widely used for cancer therapy. Epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of Triple-negative breast cancer (TNBC) patients. Although Cetuximab, which targets EGFR, has shown some inhibitory effects on TNBC cells, Cetuximab resistance cases due to ligand-independent activating mutations in the EGFR gene limit its application. Due to various benefits of single chain antibodies (scFvs), the use of these antibodies in cancer targeted therapy is increasing. In this study, a specific anti-EGFR antibody was isolated and evaluated. Methods: Panning procedure was used against an immunodominant epitope of EGFR in its dimerization arm using a diverse phage library. Polymerase Chain Reaction (PCR) and fingerprinting were applied to identify the specific clones. The MTT tetrazolium assay was performed to evaluate the inhibitory effects of selected anti-EGFR scFv phage antibody on MDA-MB-468, a TNBC cell line. Results: After four round of panning, one dominant pattern was observed in DNA fingerprinting with frequency of 85%. The growth of MDA-MB-468 cells was decreased dose-dependently after treatment with anti-EGFR scFv phage antibody. No significant inhibitory effect of M13KO7 helper phage as negative control on the cell growth of MDA-MB-468 was observed (p> 0.05). Conclusions:The selected anti-EGFR scFv with high anti proliferative effect on TNBC cells offers an effective alternative for TNBC targeted therapy. The antibody, which binds to the dimerization arm of EGFR and inhibits EGFR dimerization, could also overcome TNBC cases with Cetuximab resistance due to ligandindependent activating mutations.

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“…With respect to FZD7, the vast majority of studies focused on breast cancer, in particular triple-negative breast cancer (TNBC), for TNBC was unresponsive to classical endocrine therapy. FZD7 was thus considered as one of the important therapeutic targets in TNBC and showed an improved therapeutic e cacy as well [26][27][28][29][30]. However, little is known about the role of FZD7 in PAAD to date.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

Liu

Zhang

2020

Preprint

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Background: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. we aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management.Methods: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (x64 3.6.2) were used to comprehensively analyze the roles of FZDs. p-value below to 0.05 was considered as significant difference.Results: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. PAAD patients with high expression of FZD6 had shorter overall survival (OS) than those with low expression, indicating that FZD6 could be a potential prognostic and predictive marker in PAAD. PAAD patients with high expression of FZD8 had shorter recurrence free survival (RFS) than those with low expression, indicating that FZD8 could be a potential therapeutic target in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3, 4, 5, 6, and 9 could be potential prognostic and predictive markers, and FZD4 and 8 might function as potential therapeutic targets in PAAD.

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Cell growth inhibition and apoptosis in breast cancer cells induced by anti-FZD7 scFvs: involvement of bioinformatics-based design of novel epitopes

Cited by 14 publications

References 35 publications

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

Anti-Proliferative Effect of Specific Anti-EGFR Single Chain Antibody on Triple Negative Breast Cancer Cells

Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

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