Platelet-derived growth factor expression and stimulation in human meningiomas.
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.
Black
P M
PM
Brain Tumor Center, Brigham and Women's Hospital, Boston, Massachusetts.
Carroll
R
R
Glowacka
D
D
Riley
K
K
Dashner
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077214:Becaplermin; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008579:Meningioma / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D016761:Oncogene Proteins v-fos; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor