Development of a xenograft glioma model in mouse brain.

Xenograft intracerebral glioma models have been developed in normal mice by growing the rat C6 glioma in either adult or neonatal mouse brains. Using this tumor line it was possible to grow discrete intracerebral gliomas in either CBA or AKR adult mice or neonatal mice. The size of the tumor mass and length of survival was directly related to the number of tumor cells injected and the time after implantation. To obtain localized intracranial tumor growth cells were suspended in a 1% agarose solution before implantation. Following injection of 10(6) cells into the frontal lobe of adult CBA or AKR mice, discrete tumor masses greater than 4 mm in diameter were obtained in 90% of animals at 14 days, and the largest tumors in adult mice occurred between 21 and 28 days after implantation. The tumor size following implantation of 10(6) cells was significantly greater than with 10(5) cells at 7 days (P less than 0.05) and at 14 and 21 days (P less than 0.01). Less than 60% of mice of BALB/c, RIII, or C57 black strains developed tumors greater than 4 mm diameter at 14 days after intracerebral injection of 10(6) C6 cells. Using neonatal mice it was found that when 10(5) cells were injected intracranially tumors greater than 4 mm in diameter developed in 14 of 15 animals within 2 weeks (CBA mice). Similar results were seen in the RIII, AKR, C57 black, and BALB/c strains. Longer growth periods resulted in larger tumors, up to 8 mm in diameter (6 of 10 animals at 20 days). The tumors in the neonatal animals were not as discrete as in the adult mice, and tumor often spread to the meninges and into the lateral ventricles. The tumor harvested from the brain had a cloning efficiency of 1.2 +/- 0.4% (SD). A panel of monoclonal antibodies was raised to the C6 glioma, and this was used to define clearly the margins of the tumor within the brain. The xenograft mouse models should prove useful for the study of the therapy of gliomas.