Ellis Jason A, Castelli Michael, Assanah Marcela, Bruce Jeffrey N, Canoll Peter, Ogden Alfred T
Department of Neurological Surgery, Neurological Institute of New York, Columbia University Medical Center, 710 West 168th Street, New York, NY, 10032, USA,
J Neurooncol. 2015 May;123(1):27-33. doi: 10.1007/s11060-015-1769-2. Epub 2015 Apr 14.
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.
将表达血小板源性生长因子B（PDGF-B）的逆转录病毒注射到成年大鼠的皮质下白质中，会诱导快速形成具有胶质母细胞瘤组织学特征的脑肿瘤。相比之下，当将相同的逆转录病毒注射到成年大鼠的脊髓中时，所产生的肿瘤生长较为缓慢，并且呈现出独特的组织学特征，其特点是肿瘤细胞巢被密集的血管网络分隔开，且无坏死区域。为了研究这些差异是由肿瘤起源细胞决定还是受微环境影响，我们进行了一系列移植实验。分别从PDGF诱导的脑肿瘤和脊髓肿瘤中分离细胞，然后将其移植到未经处理的大鼠前脑和脊髓中。通过组织学分析、标志物表达谱分析、PDGFR亚型分析以及肿瘤诱发发病的潜伏期对所产生的肿瘤进行特征描述。发现肿瘤表型始终由移植的组织而非起源组织所预测。这些结果表明，在本模型中，肿瘤微环境而非肿瘤起源细胞可能是胶质瘤表型的主要决定因素。
