Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas

Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineag e, 501, containing a liver alpha-amylase promoted-SV40 Tag hybrid gene, rou tinely develop SV40 Tag-induced metastatic osteosarcomas. This form of alph a-amylase was known to be expressed in the liver, salivary glands, pancreas , and fat. Cells in the normal rib adjacent to the periosteum also express alpha-amylase suggesting that transgene expression is correctly targeted to generate osteosarcomas. 501 mice express SV40 Tag in the salivary glands b ut do not develop abnormalities in these organs by the time of their death from SV40-induced osteosarcomas. Mice of the C57BL/6 strain make a strong a nd effective anti-tumor immune response to SV40 Tag immunization. However, immunization of 501 mice with SV40 Tag early in life does not alter or prev ent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a significantly le ss effective cytotoxic T-lymphocyte response following SV40 Tag immunizatio n while 501 osteosarcoma-derived cells are fully susceptible to SV40 Tag-sp ecific T-cell lysis. This suggests that partial tolerance, not loss of anti gen presentation by tumor cells, characterizes this mouse model of endogeno us bone tumor development. To determine whether the immune recognition of e ndogenous SV40 Tag could influence tumorigenesis, the metastatic potential and time of death from tumor was investigated in CD4-null mutant 501 mice a nd beta-2 microglobulin-null mutant 501 mice. The size and number of metast ases in these strains and longevity of these strains varied. We suggest tha t components of both the innate and adaptive immune response control tumor appearance and progression.