Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines.
Glioma cells in culture express platelet-derived growth factor (PDGF) A- and B-chains and secrete PDGF-like activity that is mainly PDGF-AA. In this work, we show that the PDGF alpha- and beta-receptors are independently expressed in human malignant glioma cells. We also define three different receptor phenotypes that are related to the morphology of glioma cells: cells with only alpha-receptors, only beta-receptors, or with both types of receptors. By the help of Northern blot analyses, 125I-PDGF-binding experiments, and immunoprecipitations the receptors are shown to be structurally normal PDGF receptors, except for minor variations in size that probably are due to differences in glycosylation. PDGF-BB induces DNA synthesis in cells of all three receptor phenotypes, whereas PDGF-AA or PDGF-AB has this effect only on cells with alpha- or with alpha- and beta-receptors. 125I-PDGF-AB binds with high affinity and down-regulates beta-receptors only in cells where alpha-receptors are present in addition to beta-receptors. Thus, the different functional capacities of PDGF isoforms on glioma cells fit with their known receptor-binding specificities and are compatible with the hypothesis that the isoforms act by inducing dimeric receptor complexes. When data on PDGF A- and B-chains, as well as alpha- and beta-receptor expression are compiled and the pattern of receptor binding specificity is taken into account, the majority of glioma cell lines are found to have a phenotype that makes autocrine stimulation possible.
Nistér
M
M
Department of Pathology, University Hospital, Uppsala, Sweden.
Claesson-Welsh
L
L
Eriksson
A
A
Heldin
C H
CH
Westermark
B
B
D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005910:Glioma; D006801:Humans; D010641:Phenotype; D010982:Platelet-Derived Growth Factor; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor