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Platelet-derived growth factor expression and stimulation in human meningiomas

Authors: P M, Black; R, Carroll; D, Glowacka; K, Riley; K, Dashner;

Platelet-derived growth factor expression and stimulation in human meningiomas

Abstract

✓ The platelet-derived growth factor (PDGF) family consists of subunits A and B and receptors α and β. This paper evaluates the potential role of the homodimer PDGF-BB as a growth factor in meningiomas. It analyzes the expression of messenger RNA in members of the PDGF family in these tumors, measures the growth response of meningiomas to exogenous PDGF-BB in culture, and examines the induction of the c-fos proto-oncogene by PDGF-BB. Northern blot analysis was carried out on tissue from 20 meningiomas to measure the expression of PDGF-A, PDGF-B, PDGF-α receptor (PDGF-α-R) and PDGF-β receptor (PDGF-β-R). All tumors expressed PDGF-A and PDGF-B subunits. Nineteen of the 20 tumors expressed PDGF-β-R and none expressed PDGF-α-R as measured by this technique. Because the β receptor is selectively sensitive to stimulation by the PDGF-B subunit, these data suggest that meningiomas might be susceptible to stimulation by PDGF-BB. To test this hypothesis, the effect of exogenous PDGF-BB on meningioma growth was evaluated by incubating cells from 10 human meningiomas. Tritiated thymidine incorporation was used to evaluate stimulation of growth over a 48-hour period using PDGF-BB concentrations of 1, 3, or 6 ng/ml. Linear regression analysis and multiple-factor analysis of variance were used to measure PDGF-BB effects. Three of the 10 tumor specimens responded significantly to PDGF-BB, with a three- to sixfold increase in thymidine incorporation over 72 hours of exposure, and there was a significant overall growth-stimulating effect of PDGF-BB in the 10 tumor specimens tested. In the last set of experiments, the functionality of the PDGF-β-R was determined by examining the induction of the proto-oncogene c-fos by PDGF-BB in meningioma cell cultures. A significant increase in c-fos protein was observed 3 hours after PDGF-BB addition. These findings demonstrate that PDGF-A, PDGF-B, and PDGF-β-R are expressed in meningiomas and suggest that the β receptor is functional: when it is activated, c-fos levels are increased, and an increase in meningioma cell division is observed after the addition of PDGF-BB. These studies support the hypothesis that PDGF acts as a growth factor in meningiomas.

Related Organizations
Keywords

Adult, Aged, 80 and over, Male, Platelet-Derived Growth Factor, Becaplermin, Proto-Oncogene Proteins c-sis, Middle Aged, Proto-Oncogene Mas, Oncogene Proteins v-fos, Proto-Oncogene Proteins, Linear Models, Meningeal Neoplasms, Tumor Cells, Cultured, Humans, Female, Receptors, Platelet-Derived Growth Factor, RNA, Messenger, RNA, Neoplasm, Meningioma, Aged

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    Top 10%
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    Top 10%
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
94
Top 10%
Top 10%
Top 10%