ABSTACT Wnt/β-catenin signaling pathway through Frizzled receptors has been shown to play a key role in both normal development and tumorigenesis. Overexpression of Wnt pathway genes, such as Fzd7 in several malignancies is well-documented. Therefore, targeting of Fzd7 and its ligand inhibits cancer cells proliferation metastasis. In the present study we isolated single chain variable fragments (scFvs) against Fzd7 receptor using phage display method. Semi-synthetic human naive antibody libraries (Tomlinson I + J) was employed in panning procedure to isolate specific scFv against specific peptide from extracellular domain of Fzd7 receptor. The reactivity and growth inhibition effects of the selected antibodies was evaluated using enzyme-linked immunosorbent assay (ELISA), MTT and annexin V assays, respectively. Seven scFvs reactive to Fzd7 were selected following 4 rounds of panning. The results showed that the selected scFvs inhibits cell growth through apoptosis cell death in a triple negative breast cancer cells, MDA-MB-231. Given that Fzd7 and Wnt pathway plays a critical role in tumor progression, selected blocking scFvs represent significant potential for immunotherapy of breast cancer cells.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639855 | PMC |
http://dx.doi.org/10.1080/21655979.2016.1255383 | DOI Listing |
Stem Cell Reports
December 2024
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address:
During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs).
View Article and Find Full Text PDFJ Biomed Mater Res A
January 2025
Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other breast cancer subtypes. One factor contributing to this poor prognosis is that TNBC lacks expression of the receptors that available hormonal or molecular-oriented therapies attack. New treatments that exploit biological targets specific to TNBC are desperately needed to improve patient outcomes.
View Article and Find Full Text PDFBiophys J
December 2024
Program in Integrative Nutrition & Complex Diseases, Texas A&M University, College Station, Texas; Department of Nutrition, Texas A&M University, College Station, Texas; CPRIT Regional Center of Excellence in Cancer Research, Texas A&M University, College Station, Texas. Electronic address:
Cholesterol-enriched plasma membrane domains are known to serve as signaling platforms in a diverse array of cellular processes. However, the link between cholesterol homeostasis and mutant APC-KRas-associated colorectal tumorigenesis remains to be established. Thus, we investigated the impact of Apc-Kras on 1) colonocyte plasma membrane cholesterol homeostasis, order, and receptor nanoclustering, 2) colonocyte cell proliferation, and 3) whether these effects are modulated by select membrane active dietaries (MADs).
View Article and Find Full Text PDFJ Med Chem
December 2024
Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, Stockholm S-171 77, Sweden.
The Frizzled family (FZD) of G protein-coupled receptors regulates WNT signaling mediating proliferative input. Dysregulation of FZD and exaggerated WNT/β-catenin signaling is frequently observed in intestinal cancers. Therefore, it is attractive to develop therapeutics targeting FZD for cancer treatment.
View Article and Find Full Text PDFLife Sci
December 2024
The Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem Cell Biology of Hunan Province, and Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha, Hunan 410013, China; Institute of Interdisciplinary Studies, Hunan Normal University, Hunan 410081, China. Electronic address:
Aims: The dysregulated Wnt/β-Catenin signaling pathway leads to occurrence of various diseases, and abnormal activation of β-Catenin is a major characteristic of human HCC. FZD7 is a positive regulator of the Wnt/β-catenin signaling pathway, and its upregulation is related to increase of β-catenin expression and carcinogenesis in human HCC. However, mechanisms underlying FZD7 upregulation in HCC remain elusive.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!