ANTITUMOR ACTIVITY OF BACTERIOPHAGES IN MURINE EXPERIMENTAL CANCER MODELS CAUSED POSSIBLY BY INHIBITION OF β3 INTEGRIN SIGNALING PATHWAY

Bacteriophages (phages) as bacterial viruses are generally believed to have no intrinsic tropism for mammalian cells. In this study the interactions between phages and various eukaryotic cells were investigated. Binding of phages to the membranes of cancer and normal blood cells was observed. Moreover, it was shown that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity for melanoma cells inhibit markedly and significantly experimental lung metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible molecular mechanism of these effects, namely a specific interaction between the LysGly-Asp motif of the phage protein 24 and beta 3-integrin receptors on target cells is proposed. It was also shown that anti-beta 3 antibodies and synthetic peptides mimicking natural beta 3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described beta 3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of beta 3 integrins by phage preparations results in a significant decrease in tumor invasiveness.