lacZ-neoR transfected glioma cells in syngeneic rats: Growth pattern and characterization of the host immune response against cells transplanted inside and outside the CNS

Therese Visted, Jon Thorsen, Frits Thorsen, Tracy Ann Read, Elling Ulvestad, Olav Engebraaten, Dag SØrensen, Seppo Ylä-Herttuala, Kristina Tyynela, Garry Rucklidge, Klaus Edvardsen, Rolf Bjerkvig, Morten Lund-Johansen

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The rat glioma cell lines BT4C and BT4Cn were stably transfected with the bacterial lacZ-neomycin resistance (neoR) gene construct. Both transfected (BT4ClacZ and BT4CnlacZ) and untransfected cell lines were injected intracerebrally and subcutaneously into rats. Survival time, morphology, growth rate and immunological properties of the tumors were studied. Survival time was significantly prolonged after intracerebral implantation of the transfected cell lines. No similar response was found in nude rats, indicating an immunological response towards the lacZ-neoR- transfected cells in immunocompetent animals. Morphological observations showed that the lacZ-neoR-transfected gliomas were smaller and had a distinct boundary with the normal brain tissue, whereas the parental cell lines revealed a more diffuse growth pattern. Immunostaining showed a higher proportion of immunocompetent cells infiltrating the lacZ-neoR-transfected tumors. After s.c. injection, the lacZ-neoR-transfected BT4C cell line had a prolonged lag phase before assuming a growth rate similar to that of the parental cells. The BT4CnvlacZ tumors initially grew fastest, but then disappeared within 3 weeks. A similar response was observed with mock- transfected tumor cells. A 3HTdR-incorporation assay on spleen cells from rats transplanted s.c. with BT4CnvlacZ cells showed a 10-fold increase in cell activation as compared with rats with BT4Cn tumors. A humoral response towards the transfected cells was verified by Western-blot analyses.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalInternational Journal of Cancer
Volume85
Issue number2
DOIs
StatePublished - Jan 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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