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

The rat glioma cell lines BT4C and BT4Cn were stably transfected with the b acterial lacZ-neomycin resistance (neoR) gene construct. Both transfected ( BT4ClacZ and BT4CnlacZ) and untransfected cell lines were injected intracer ebrally and subcutaneously into rats. Survival time, morphology, growth rat e and immunological properties of the tumors were studied. Survival time wa s significantly prolonged after intracerebral implantation of the transfect ed cell lines. No similar response was found in nude rats, indicating an im munological response towards the lacZ-neoR-transfected cells in immunocompe tent animals. Morphological observations showed that the lacZ-neoR-transfec ted gliomas were smaller and had a distinct boundary with the normal brain tissue, whereas the parental cell lines revealed a more diffuse growth patt ern. Immunostaining showed a higher proportion of immunocompetent cells inf iltrating 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 i nitially grew fastest, but then disappeared within 3 weeks. A similar respo nse was observed with mock-transfected tumor cells. A (3)HTdR-incorporation assay on spleen cells from rats transplanted s.c. with BT4CnvlacZ cells sh owed a 10-fold increase in cell activation as compared with rats with BT4Cn tumors. A humoral response towards the transfected cells was verified by W estern-blot analyses. Int. J Cancer 85:228-235 (C) 2000 Wiley-Liss, Inc.