Growth, morphology, and serial transplantation of anaplastic human gliomas in athymic mice

Sixteen of 17 anaplastic human gliomas (AHGs) transplanted into athymic mice produced progressively growing subcutaneous nodules at the site of implantation. Thirty-four of 68 animals (50%) receiving transplanted tissue developed 500 m3 tumors in 24 to 364 days. Fourteen AHG were passed to a second animal generation, and 11 showed continued growth. Eight of these were serially passed, with one reaching a sixth animal generation, four reaching a fifth, and a three third. Once growth occurred in a second animal generation, no AHGs were lost in subsequent passages because of failure to grow. Of 234 animals receiving tumors beyond the first animal generation, 189 (80.8%) developed tumors. Average doubling times of the exponentially growing tumors in serial passage ranged from 3.0 to 19.1 days. This growth rate tended to increase and stabilize in early animal passages. The tumors growing in animals contained cell types which were present in the original human tumors, including fibrillary and protoplasmic astrocytes, small anaplastic cells, gemistocytes, anaplastic spindle cells, and multinucleate giant cells. Glial fibrillary acidic protein (GFAP) was detected in 15 of 17 biopsy specimens and in 12 of 14 AHGs in animals. These data illustrate the value of the athymic mouse system for the investigation of human brain tumors by demonstrating a high rate of successful transplantation, quantitative growth data on serially passed tumors, and morphological and immunochemical resemblance of the tumors in mice to the original human tumors.