Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin C H, Westermark B, Nistér M
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Cancer Res. 1992 Jun 1;52(11):3213-9.
The expression of platelet-derived growth factor (PDGF) and its receptors was analyzed in 14 gliomas of various degrees of malignancy and compared with three gliosis cases by in situ hybridization and immunohistochemistry techniques. Expression of both PDGF A- and B-chains was higher in glioblastomas than in astrocytomas. The PDGF A-chain mRNA was predominantly found in cell-rich areas in glioblastomas. The cognate PDGF-alpha receptor (PDGFR-alpha) mRNA was heterogeneously distributed in gliomas of all grades, and PDGFR-alpha expression was higher in gliomas than in gliosis. Within some glioblastomas probed with PDGFR-alpha complementary RNA, cells heavily loaded with grains were intermingled with others containing low or moderate signals. The heavily labeled cells were often found in the vicinity of proliferating capillaries. Immunostaining with an anti-PDGF antibody and an affinity-purified antiserum against the PDGFR-alpha showed strong staining of most tumor cells with both antibodies in glioblastoma. In addition, the PDGFR-alpha antibodies yielded a strong staining of scattered cells, and the anti-PDGF antibody yielded staining of a few cells within the astrocytoma. Furthermore, high levels of the PDGF-beta receptor (PDGFR-beta) and PDGF B-chain mRNA as well as the beta receptor protein were found in hyperplastic capillaries. These results suggest the presence of autocrine and paracrine loops in glioma, activating the PDGFR-alpha in glioma cells and the PDGFR-beta in endothelial cells.
采用原位杂交和免疫组化技术，对14例不同恶性程度的胶质瘤中血小板衍生生长因子（PDGF）及其受体的表达进行了分析，并与3例胶质增生病例进行了比较。胶质母细胞瘤中PDGF A链和B链的表达均高于星形细胞瘤。PDGF A链mRNA主要见于胶质母细胞瘤中细胞丰富的区域。同源的PDGF-α受体（PDGFR-α）mRNA在各级胶质瘤中呈异质性分布，且PDGFR-α在胶质瘤中的表达高于胶质增生。在一些用PDGFR-α互补RNA探针检测的胶质母细胞瘤中，大量携带颗粒的细胞与其他含有低或中等信号的细胞混合存在。大量标记的细胞常出现在增殖毛细血管附近。用抗PDGF抗体和抗PDGFR-α亲和纯化抗血清进行免疫染色显示，胶质母细胞瘤中的大多数肿瘤细胞用这两种抗体均呈强染色。此外，PDGFR-α抗体对散在细胞呈强染色，抗PDGF抗体对星形细胞瘤内的少数细胞呈染色。此外，在增生的毛细血管中发现高水平的PDGF-β受体（PDGFR-β）和PDGF B链mRNA以及β受体蛋白。这些结果提示胶质瘤中存在自分泌和旁分泌环，激活胶质瘤细胞中的PDGFR-α和内皮细胞中的PDGFR-β。
