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

I. Márton, Susan E. Johnson, Ivan Damjanov, Karen S. Currier, John P. Sundberg, Barbara B. Knowles

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineage, 501, containing a liver α-amylase promoted-SV40 Tag hybrid gene, routinely develop SV40 Tag-induced metastatic osteosarcomas. This form of α-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 α-amylase suggesting that transgene expression is correctly targeted to generate osteosarcomas. 501 mice express SV40 Tag in the salivary glands but 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 and effective anti-tumor immune response to SV40 Tag immunization. However, immunization of 501 mice with SV40 Tag early in life does not alter or prevent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a significantly less effective cytotoxic T-lymphocyte response following SV40 Tag immunization while 501 osteosarcoma-derived cells are fully susceptible to SV40 Tag-specific T-cell lysis. This suggests that partial tolerance, not loss of antigen presentation by tumor cells, characterizes this mouse model of endogenous bone tumor development. To determine whether the immune recognition of endogenous SV40 Tag could influence tumorigenesis, the metastatic potential and time of death from tumor was investigated in CD4-null mutant 501 mice and β-2 microglobulin-null mutant 501 mice. The size and number of metastases in these strains and longevity of these strains varied. We suggest that components of both the innate and adaptive immune response control tumor appearance and progression.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalTransgenic Research
Volume9
Issue number2
DOIs
Publication statusPublished - 2000

Fingerprint

osteosarcoma
Osteosarcoma
Transgenic Mice
genetically modified organisms
mice
Amylases
Immunization
amylases
Neoplasms
Salivary Glands
Inbred C57BL Mouse
immunization
neoplasms
salivary glands
Periosteum
Liver
Bone Development
Antigen Presentation
Cytotoxic T-Lymphocytes
Adaptive Immunity

Keywords

  • α-amylase expression in salivary glands and ribs
  • Metastatic osteogenic sarcoma
  • Role of CD4 and β-2 microglobulin in SV40 Tag tumors
  • SV40 Tag tumor immunity
  • Tolerance to endogenous tumor antigens

ASJC Scopus subject areas

  • Genetics
  • Plant Science
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Biotechnology
  • Food Science

Cite this

Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. / Márton, I.; Johnson, Susan E.; Damjanov, Ivan; Currier, Karen S.; Sundberg, John P.; Knowles, Barbara B.

In: Transgenic Research, Vol. 9, No. 2, 2000, p. 115-125.

Research output: Contribution to journalArticle

Márton, I. ; Johnson, Susan E. ; Damjanov, Ivan ; Currier, Karen S. ; Sundberg, John P. ; Knowles, Barbara B. / Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. In: Transgenic Research. 2000 ; Vol. 9, No. 2. pp. 115-125.
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