The goal of this research is to examine the role of adhesion molecules and lymphocyte homing in the migration of virally infected lymphocytes from the gut to the mammary gland in MMTV infection. The contribution of homing molecules such as L-selectin and beta7 integrin to viral infection and spread will be studied by a variety of methods including available knockout mouse strains, as well as the administration of blocking monoclonal antibodies. Homing molecule-deficient mice will acquire MMTV either by nursing on viremic mothers, or by injection. First, the lactating mammary gland will be defined in terms of the presence of lymphocytes and the expression of homing and adhesion molecules by FACS analysis and immunohistochemistry. The ability of the virus to travel to the mammary tissue in the presence or absence of adhesion molecules will be studied using a sensitive RNAse protection assay to determine MMTV levels in lactating mammary tissue, and the mil present in the stomachs of newborn pups. PCR and immunohistochemistry will be used to determine viral infection or peripheral lymphoid tissues such as spleen, lymph nodes, and thymus. These studies will define the homing and adhesion molecular important in the migration of MMTV-infected lymphocytes and subsequent tumor development. This research should be relevant to human malignancies such as HTLV and T cell lymphomas as both of these cancers have been shown to express large amounts of beta7 integrin. Overall, this system will allow the study of a variety of aspects of cancer such as, mechanisms of tumorigenesis, tumor spread, tumor immunology, and possible targets for intervention.
| Czarneski, Jennifer; Rassa, John C; Ross, Susan R (2003) Mouse mammary tumor virus and the immune system. Immunol Res 27:469-80 |
| Czarneski, Jennifer; Berguer, Paula; Bekinschtein, Pedro et al. (2002) Neonatal infection with a milk-borne virus is independent of beta7 integrin- and L-selectin-expressing lymphocytes. Eur J Immunol 32:945-56 |
| Czarneski, J; Meyers, J; Peng, T et al. (2001) Interleukin-4 up-regulates mouse mammary tumor virus expression yet is not required for in vivo virus spread. J Virol 75:11886-90 |
