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Susceptibility of breast cancer cells to an oncolytic matrix (M) protein mutant of vesicular stomatitis virus

Cancer Gene Therapy volume 17, pages 883–892 (2010)Cite this article

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Abstract

Matrix (M) protein mutants of vesicular stomatitis virus (VSV), such as rM51R-M virus, are attractive candidates as oncolytic viruses for tumor therapies because of their capacity to selectively target cancer cells. The effectiveness of rM51R-M virus as an antitumor agent for the treatment of breast cancer was assessed by determining the ability of rM51R-M virus to infect and kill breast cancer cells in vitro and in vivo. Several human- and mouse-derived breast cancer cell lines were susceptible to infection and killing by rM51R-M virus. Importantly, non-tumorigenic cell lines from normal mammary tissues were also sensitive to VSV infection suggesting that oncogenic transformation does not alter the susceptibility of breast cancer cells to oncolytic VSV. In contrast to results obtained in vitro, rM51R-M virus was only partially effective at inducing regression of primary breast tumors in vivo. Furthermore, we were unable to induce complete regression of the primary and metastatic tumors when tumor-bearing mice were treated with a vector expressing interleukin (IL)-12 or a combination of rM51R-M virus and IL-12. Our results indicate that although breast cancer cells may be susceptible to VSV in vitro, more aggressive treatment combinations are required to effectively treat both local and metastatic breast cancers in vivo.

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Acknowledgements

We thank Griffith Parks for providing the human mammary epithelial cell lines, Hermina Borgerink for H and E staining of tissue sections and Nancy Kock for examination of tissues. This work was supported by grant BC024238 from the Department of Defense to M Ahmed and grant R01-AI032983 from the NIAID to D Lyles.

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  1. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M Ahmed, S Puckett & D S Lyles

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  1. M Ahmed
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Correspondence to M Ahmed.

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Ahmed, M., Puckett, S. & Lyles, D. Susceptibility of breast cancer cells to an oncolytic matrix (M) protein mutant of vesicular stomatitis virus. Cancer Gene Ther 17, 883–892 (2010). https://doi.org/10.1038/cgt.2010.46

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