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Acta Virologica Vol.48, p.241-248, 2004 |
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Title: ANTITUMOR ACTIVITY OF BACTERIOPHAGES IN MURINE EXPERIMENTAL CANCER MODELS CAUSED POSSIBLY BY INHIBITION OF b3 INTEGRIN SIGNALING PATHWAY | ||
Author: K. DABROWSKA, A. OPOLSKI, J. WIETRZYK, K. SWITALA-JELEN, J. BORATYNSKI, A. NASULEWICZ, L. LIPINSKA, A. CHYBICKA, M. KUJAWA, M. ZABEL, B. DOLINSKA-KRAJEWSKA, E. PIASECKI, B. WEBER-DABROWSKA, J. RYBKA, J. SALWA, E. WOJDAT, M. NOWACZYK, A. GORSKI | ||
Abstract: 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 Lys-Gly-Asp motif of the phage protein 24 and b3-integrin receptors on target cells is proposed. It was also shown that anti-b3 antibodies and synthetic peptides mimicking natural b3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described b3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of b3 integrins by phage preparations results in a significant decrease in tumor invasiveness. |
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Keywords: phage T4; melanoma; antimetastatic activity; b3-integrins | ||
Year: 2004, Volume: 48, Issue: | Page From: 241, Page To: 248 | |
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