Unique microenvironmental responses to PDGF stimulation in brain and spinal cord gliomas determine tumor phenotype

Jason A. Ellis, Michael Castelli, Marcela Assanah, Jeffrey N. Bruce, Peter Canoll, Alfred T. Ogden

Injection of a PDGF-B expressing retrovirus into the subcortical white matter of adult rats induces the rapid formation of brain tumors that have the histological features of glioblastoma. In contrast, when the same retrovirus is injected into the spinal cord of adult rats the resulting tumors are more indolent and display a unique histology characterized by nests of tumor cells separated by a dense vascular network without areas of necrosis. To study whether these differences are determined by the tumor cell of origin or due to microenvironmental influences, we conducted a series of transplantation experiments. Cells were independently isolated from PDGF-induced brain and cord tumors then subsequently transplanted into naive rat forebrains and spinal cords. The resulting tumors were characterized by histological analysis, marker expression profiling, PDGFR subtyping, and latency to tumor-induced morbidity. Tumor phenotypes were found to be consistently predicted by the tissue into which they were transplanted rather than by the tissue of origin. These results suggest that tumor microenvironment rather than the tumor cell of origin may be the primary determinant of glioma phenotype in the model presented.