Exposure to Bacteriophages T4 and M13 Increases Integrin Gene Expression and Impairs Migration of Human PC-3 Prostate Cancer Cells

Abstract

The interaction between bacteriophages and integrins has been reported in different cancer cell lines, and efforts have been undertaken to understand these interactions in tumor cells along with their possible role in gene alterations, with the aim to develop new cancer therapies. Here, we report that the non-specific interaction of T4 and M13 bacteriophages with human PC-3 cells results in differential migration and varied expression of different integrins. PC-3 tumor cells (at 70% confluence) were exposed to 1 × 107 pfu/mL of either lytic T4 bacteriophage or filamentous M13 bacteriophage. After 24 h of exposure, cells were processed for a histochemical analysis, wound-healing migration assay, and gene expression profile using quantitative real-time PCR (qPCR). qPCR was performed to analyze the expression profiles of integrins ITGAV, ITGA5, ITGB1, ITGB3, and ITGB5. Our findings revealed that PC-3 cells interacted with T4 and M13 bacteriophages, with significant upregulation of ITGAV, ITGA5, ITGB3, ITGB5 genes after phage exposure. PC-3 cells also exhibited reduced migration activity when exposed to either T4 or M13 phages. These results suggest that wildtype bacteriophages interact non-specifically with PC-3 cells, thereby modulating the expression of integrin genes and affecting cell migration. Therefore, bacteriophages have future potential applications in anticancer therapies.

APTC-C-SA01: A Novel Bacteriophage Cocktail Targeting Staphylococcus aureus and MRSA Biofilms

“…Bacteriophages (phages) were considered an effective antimicrobial as early as the 1920s and have recently regained interest for their potential to treat infections with antibiotic-resistant strains including MRSA [ 27 , 28 ]. Phages have also been shown to affect the physiology of cancer cells in vitro [ 19 , 20 ] and have been shown to be effective against bacterial biofilms [ 29 , 30 , 31 , 32 ]. This latter is in line with our results where all MRSA strains tested in both planktonic and biofilm form were sensitive to at least one of the phages tested.…”

“…However, the rapid development of the antibiotic industry led to a decrease in phage usage. Now, as the current situation of drug resistance becomes more and more pressing, phages have again attracted our attention, although we still face many challenges when it comes to applying phages for clinical treatment [ 19 ]. While phages are generally considered to target specific bacterial species and leave the human host unaffected, phages have also recently been shown to affect the expression of mammalian genes and the pathophysiology of cancer cells in vitro [ 19 , 20 ].…”

“…Now, as the current situation of drug resistance becomes more and more pressing, phages have again attracted our attention, although we still face many challenges when it comes to applying phages for clinical treatment [ 19 ]. While phages are generally considered to target specific bacterial species and leave the human host unaffected, phages have also recently been shown to affect the expression of mammalian genes and the pathophysiology of cancer cells in vitro [ 19 , 20 ]. While further research is required to validate such effects in relevant in vivo models, these findings warrant further investigations into the potential use of phages as an adjuvant to anticancer therapies.…”

Bacterial RNA virus MS2 exposure increases the expression of cancer progression genes in the LNCaP prostate cancer cell line

“…Based on our previously reported work with PC3 and LNCaP cells and their interactions with T4 and M13 phage (19)(20)(21)(22)(23); we found that LNCaP cells more closely represent metastasis Prostate cancer than PC3 cells due to their androgen independence. Hence, we selected LNCaP cells for MS2 phage interaction studies.…”

“…Hence in the present study, key findings relating to the interaction of the natural bacteriophage, MS2, with the PCa cell line, LNCaP, were reported. Considering the importance of bacteriophages for natural phage therapy and previous reports of the interaction of T4 and M13 bacteriophages with PCa cell lines (PC3 and LNCaP) affecting cell migration and viability and modulating genes for cancer progression (19)(20)(21)(22)(23), the present study is of great importance to understand the direct effects of bacterial RNA viruses on PCa cell progression. Their effects on cell viability and genes that are involved in cancer cell proliferation [such as AR, AKT, PI3K, MAPK1, MAPK3, heat shock protein 90 (HSP90), heat shock protein 27 (HSP27), and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1A)], and adhesion, migration, and invasion [such as integrins; integrin α5 (ITGA5), integrin αV (ITGAV), integrin β1 (ITGB1), integrin β3 (ITGB3) and integrin β5 (ITGB5)] were investigated.…”