Xenograft of human malignant glial tumors into brains of nude mice. A histopatholgical study.

Sixteen of 21 human malignant glial tumors were successfully heterotransplanted into the brains of nude mice, and one other was transplanted into the brain after prior subcutaneous heterotransplantation. Most xenografts grew preferentially as diffusely infiltrating tumors within hemispheric white matter, generally sparing cortex and deep gray matter. The heterogeneity of most in vivo human tumors gave way to a tumor of generally uniform cell type while growing in nude mice. From six human tumors, all glioblastomas, there emerged histologic patterns or cell forms that were not evident in the original tumor. Tumors from 15 patients were treated with standard chemotherapeutic agents while growing in nude mouse brains. The most common morphologic change induced in tumors by several agents was a distinctive giant cell change characterized by large bizarre nuclei and abundant cytoplasm. It is concluded that the human brain-tumor-nude-mouse xenograft model offers morphological parallels with the clinical situation, but selects for growth only some of the many subpopulations of the human tumor. Such selection imposes restriction on the clinical inferences that may be drawn from this model.