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Open Access Research article

Exacerbated metastatic disease in a mouse mammary tumor model following latent gammaherpesvirus infection

Vinita S Chauhan, Daniel A Nelson, Lopamudra Das Roy, Pinku Mukherjee and Kenneth L Bost*

  • * Corresponding author: Kenneth L Bost klbost@uncc.edu

  • † Equal contributors

Author Affiliations

Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, North Carolina, USA

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Infectious Agents and Cancer 2012, 7:11  doi:10.1186/1750-9378-7-11

Published: 29 May 2012

Abstract

Background

Controversy exists as to the ability of human gammaherpesviruses to cause or exacerbate breast cancer disease in patients. The difficulty in conducting definitive human studies can be overcome by investigating developing breast cancer in a mouse model. In this study, we utilized mice latently infected with murine gammaherpesvirus 68 (HV-68) to question whether such a viral burden could exacerbate metastatic breast cancer disease using a mouse mammary tumor model.

Results

Mice latently infected with HV-68 had a similar primary tumor burden, but much greater metastatic disease, when compared to mock treated mice given the transplantable tumor, 4 T1. This was true for lung lesions, as well as secondary tumor masses. Increased expression of pan-cytokeratin and VEGF-A in tumors from HV-68 infected mice was consistent with increased metastatic disease in these animals. Surprisingly, no viral particles could be cultured from tumor tissues, and the presence of viral DNA or RNA transcripts could not be detected in primary or secondary tumor tissues.

Conclusions

Latent HV-68 infection had no significant effect on the size of primary 4 T1 mammary tumors, but exacerbated the number of metastatic lung lesions and secondary tumors when compared to mock treated mice. Increased expression of the tumor marker, pan-cytokeratin, and VEGF-A in tumors of mice harboring latent virus was consistent with an exacerbated metastatic disease. Mechanisms responsible for this exacerbation are indirect, since no virus could be detected in cancerous tissues.

Keywords:
Breast cancer; Mammary tumor; Metastasis; Gammaherpesvirus