Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein

Abstract

Background The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. Methods The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. Results By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. Conclusions The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

Identification of Potential Breast Cancer Stem Cell Biomarkers in the Secretome Using a Network Interaction Approach Analysis

“…Knocking down OCLN in breast cancer cell lines results in reduced cell-cell adhesion, decreased sensitivity to apoptotic signals, induction of EMT, and pertubation of Ca2+ homeostasis, leading to enhanced invasiveness [32]. Another tight junction protein, F11 Receptor (F11R), also known as Junctional Adhesion Molecule-A (JAM-A) can serve as a cell surface marker for characterizing TNBC cancer stem cells [33]. It has been reported that F11R deficiency in the MDAMB231 cell line promotes breast cancer cell invasion [34].…”