Hermansson M, Nistér M, Betsholtz C, Heldin C H, Westermark B, Funa K
Ludwig Institute for Cancer Research, Uppsala Branch, University Hospital, Sweden.
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7748-52. doi: 10.1073/pnas.85.20.7748.
The genes for platelet-derived growth factor (PDGF) A chain, B chain/c-sis, and the PDGF receptor are expressed in human malignant glioma cell lines. In the present investigation we have studied the expression of these genes in biopsy specimens from human glioblastomas. Hyperplasia of the vascular endothelium is a prominent characteristic of human glioblastoma multiforme and simian sarcoma virus-induced gliomas in primates. RNA transfer blot analysis of biopsies from glioblastoma multiforme showed transcripts for PDGF A and B chains and the PDGF receptor. Tissue sections from this tumor examined by in situ hybridization techniques revealed that the proliferating vascular endothelial cells contained large quantities of mRNA for PDGF B chain/c-sis and its receptor and, to a lesser extent, for PDGF A chain. In contrast, the tumor cells expressed more mRNA for PDGF A chain than for PDGF B chain and PDGF receptor. The latter two were also expressed at higher levels in glioma cells than in glial cells of nontumorous human brain tissue. Thus, an autocrine stimulation by the PDGF B chain/c-sis product via its receptor, evoked by interaction with surrounding glioma cells, could be the mechanism behind the pathological proliferation of endothelial cells characteristically found in this type of malignancy.
血小板衍生生长因子（PDGF）A链、B链/c-sis以及PDGF受体的基因在人类恶性胶质瘤细胞系中表达。在本研究中，我们研究了这些基因在人类胶质母细胞瘤活检标本中的表达。血管内皮细胞增生是人类多形性胶质母细胞瘤和灵长类动物中猿猴肉瘤病毒诱导的胶质瘤的一个突出特征。对多形性胶质母细胞瘤活检标本进行的RNA转移印迹分析显示有PDGF A链和B链以及PDGF受体的转录本。通过原位杂交技术检查该肿瘤的组织切片发现，增殖的血管内皮细胞含有大量PDGF B链/c-sis及其受体的mRNA，而PDGF A链的mRNA含量较少。相比之下，肿瘤细胞表达的PDGF A链mRNA比PDGF B链和PDGF受体的更多。后两者在胶质瘤细胞中的表达水平也高于非肿瘤性人类脑组织的胶质细胞。因此，PDGF B链/c-sis产物通过其受体与周围胶质瘤细胞相互作用引发的自分泌刺激，可能是这种类型恶性肿瘤中特征性的内皮细胞病理性增殖背后的机制。
