Abstract
Cytomegalovirus (CMV) infects 40–70% of women, but infection has been reported in >95% of breast cancer patients. We investigated the consequences of these observations by infecting mice with mCMV or a negative control medium for 4 days, 11 days or 10 weeks to establish active, intermediate or latent infections, respectively. Syngeneic 4T1 or E0771 breast cancer cells were then injected into a mammary fat pad of BALB/c or C57BL/6 mice, respectively. Infection did not affect tumor growth in these conditions, but latently infected BALB/c mice developed more lung metastases. The latent mCMV infection of MMTV-PyVT mice, which develop spontaneous breast tumors, also did not affect the number or sizes of breast tumors. However, there were more tumors that were multilobed with greater blood content, which had enhanced vasculature and decreased collagen content. Most significantly, mCMV infection also increased the number and size of lung metastases, which showed a higher cell proliferation. Viral DNA was detected in breast tumors and lung nodules although viral mRNA was not. These novel results have important clinical implications since an increased metastasis is prognostic of decreased survival. This work provides evidence that treating or preventing HCMV infections may increase the life expectancy of breast cancer patients by decreasing metastasis.
Highlights
Breast cancer is the most common malignancy among women, and our inability to treat metastasis is a major cause of mortality
We examined the effect of a latent mCMV infection in a mouse model with the spontaneous growth of multiple breast tumors
The significantly higher tumor mass in latently infected BALB/c mice compared to control mice treated with phosphate-buffered saline (PBS) is probably not important since there was no significant difference between the infected mice and those treated with a UV-inactivated virus (Figure 1A)
Summary
Breast cancer is the most common malignancy among women, and our inability to treat metastasis is a major cause of mortality. A reactivation to full virus replication can occur during inflammation and stress in the aging population and in immunocompromised hosts including organ transplant recipients undergoing immunosuppressive therapies [14,15,16,17] This reactivation of HCMV infection can be life-threatening, especially in immunocompromised or critically ill patients [18]. MCMV DNA was detected in breast tumors and lung metastatic nodules from the latently infected mice, no active transcription of viral genes was detected in any of the tissues examined. These results from mouse models indicate that latent mCMV infection increases the metastasis of breast cancer cells to the lungs. Preventing or controlling the negative consequences of an HCMV infection could provide a major improvement in breast cancer treatment and patient survival
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call