Guha A, Dashner K, Black P M, Wagner J A, Stiles C D
Harvard Medical School, Boston, MA.
Int J Cancer. 1995 Jan 17;60(2):168-73. doi: 10.1002/ijc.2910600206.
Established cell lines derived from human malignant astrocytomas typically express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could form an autocrine loop. In this study, we screened for the essential components of a PDGF autocrine loop in fresh surgical isolates of human astrocytomas, using in situ hybridization and immunohistochemical techniques. Eight malignant astrocytomas (6 glioblastomas and 2 anaplastic astrocytomas), 5 low-grade astrocytomas and 4 non-neoplastic glial specimens (mesial temporal sclerosis) were evaluated. Malignant astrocytomas, and to a lesser extent low-grade astrocytomas, expressed more PDGF-A and PDGF-B than non-neoplastic glia. PDGF-alpha-receptor expression was elevated both in malignant and in low-grade astrocytomas. These data support the argument that PDGF autocrine loops contribute to the unregulated growth of human astrocytomas. Expression of PDGF and PDGF receptor in low-grade astrocytomas suggests that activation of PDGF autocrine loops may be an early event in the pathogenesis of malignant astrocytomas.
源自人类恶性星形细胞瘤的成熟细胞系通常会表达血小板衍生生长因子(PDGF)和PDGF受体的组合,这可能形成一个自分泌环。在本研究中,我们使用原位杂交和免疫组化技术,在人类星形细胞瘤的新鲜手术分离组织中筛选PDGF自分泌环的关键成分。评估了8例恶性星形细胞瘤(6例胶质母细胞瘤和2例间变性星形细胞瘤)、5例低级别星形细胞瘤和4例非肿瘤性神经胶质标本(内侧颞叶硬化症)。恶性星形细胞瘤,以及程度较轻的低级别星形细胞瘤,比非肿瘤性神经胶质表达更多的PDGF-A和PDGF-B。PDGF-α受体在恶性和低级别星形细胞瘤中均有升高表达。这些数据支持了PDGF自分泌环促进人类星形细胞瘤无节制生长这一观点。低级别星形细胞瘤中PDGF和PDGF受体的表达表明,PDGF自分泌环的激活可能是恶性星形细胞瘤发病机制中的一个早期事件。