Platelet-derived growth factor expression and stimulation in human meningiomas

J Neurosurg. 1994 Sep;81(3):388-93. doi: 10.3171/jns.1994.81.3.0388.

Abstract

The platelet-derived growth factor (PDGF) family consists of subunits A and B and receptors alpha and beta. 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-alpha receptor (PDGF-alpha-R) and PDGF-beta receptor (PDGF-beta-R). All tumors expressed PDGF-A and PDGF-B subunits. Nineteen of the 20 tumors expressed PDGF-beta-R and none expressed PDGF-alpha-R as measured by this technique. Because the beta 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-beta-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-beta-R are expressed in meningiomas and suggest that the beta 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.

MeSH terms

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

Substances

  • MAS1 protein, human
  • Oncogene Proteins v-fos
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • RNA, Neoplasm
  • platelet-derived growth factor A
  • Becaplermin
  • Receptors, Platelet-Derived Growth Factor