Platelet-derived growth factor expression and stimulation in human meningiomas

Peter McL. Black M.D., Ph.D.1, Rona Carroll Ph.D.1, Danuta Glowacka Ph.D.1, Kathleen Riley B.S.1, and Kathleen Dashner B.S.1
View More View Less
  • 1 Brain Tumor Center, Brigham and Women's Hospital, Children's Hospital, and Dana-Farber Cancer Institute; and Department of Surgery, Harvard Medical School, Boston, Massachusetts
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

✓ 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.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Peter Black, M.D., Brigham and Women's and Children's Hospitals, 75 Francis Street, Boston, Massachusetts 02115.
  • 1.

    Black PML: Meningiomas. Neurosurgery 32:643657, 1993 Black PML: Meningiomas. Neurosurgery 32:643–657, 1993

  • 2.

    Carroll R, , Glowacka D, & Dashner K, et al. : Progesterone receptor expression in meningiomas. Cancer Res 53:13121316, 1993 Carroll R, Glowacka D, Dashner K, et al: Progesterone receptor expression in meningiomas. Cancer Res 53:1312–1316, 1993

    • Search Google Scholar
    • Export Citation
  • 3.

    Chirgwin JM, , Przybyla AE, & MacDonald RJ, et al. : Isolation of biologically active ribonucleic acid from sources enriched with ribonuclease. Biochemistry 18:52945301, 1979 Chirgwin JM, Przybyla AE, MacDonald RJ, et al: Isolation of biologically active ribonucleic acid from sources enriched with ribonuclease. Biochemistry 18:5294–5301, 1979

    • Search Google Scholar
    • Export Citation
  • 4.

    Cross M, & Dexter TM: Growth factors in development, transformation, and tumorigenesis. Cell 64:271289, 1991 Cross M, Dexter TM: Growth factors in development, transformation, and tumorigenesis. Cell 64:271–289, 1991

    • Search Google Scholar
    • Export Citation
  • 5.

    Elashry-Stowers D, , Zava DT, & Speers WC, et al. : Immunocytochemical localization of progesterone receptors in breast cancer with anti-human receptor monoclonal antibodies. Cancer Res 48:64626474, 1988 Elashry-Stowers D, Zava DT, Speers WC, et al: Immunocytochemical localization of progesterone receptors in breast cancer with anti-human receptor monoclonal antibodies. Cancer Res 48:6462–6474, 1988

    • Search Google Scholar
    • Export Citation
  • 6.

    Grunberg SM, , Daniels AM, & Muensch H, et al. : Correlation of meningioma hormone receptor status with hormone sensitivity in a tumor stem-cell assay. J Neurosurg 66:405408, 1987 Grunberg SM, Daniels AM, Muensch H, et al: Correlation of meningioma hormone receptor status with hormone sensitivity in a tumor stem-cell assay. J Neurosurg 66:405–408, 1987

    • Search Google Scholar
    • Export Citation
  • 7.

    Grunberg SM, , Weiss MH, & Spitz IM, et al. : Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg 74:861866, 1991 Grunberg SM, Weiss MH, Spitz IM, et al: Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg 74:861–866, 1991

    • Search Google Scholar
    • Export Citation
  • 8.

    Guha A, & Goumnerova L: Oncogenes and growth factors in astrocytomas, in Black PM, , Schoene W, & Lampson L (eds): Astrocytomas: Diagnosis, Management, and Biology. Oxford: Blackwell, 1992, pp 211227 Guha A, Goumnerova L: Oncogenes and growth factors in astrocytomas, in Black PM, Schoene W, Lampson L (eds): Astrocytomas: Diagnosis, Management, and Biology. Oxford: Blackwell, 1992, pp 211–227

    • Search Google Scholar
    • Export Citation
  • 9.

    Harsh GR, , Keating MT, & Escobedo JA, et al. : Platelet-derived growth factor (PDGF) autocrine components in human tumor cell lines. J Neurooncol 8:112, 1990 Harsh GR, Keating MT, Escobedo JA, et al: Platelet-derived growth factor (PDGF) autocrine components in human tumor cell lines. J Neurooncol 8:1–12, 1990

    • Search Google Scholar
    • Export Citation
  • 10.

    Hermansson M, , Nistér M, & Betsholtz C, et al. : Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. Proc Natl Acad Sci USA 85:77487752, 1988 Hermansson M, Nistér M, Betsholtz C, et al: Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. Proc Natl Acad Sci USA 85:7748–7752, 1988

    • Search Google Scholar
    • Export Citation
  • 11.

    Kazumoto K, , Tamura M, & Hoshino H, et al. : Enhanced expression of the sis and c-myc oncogenes in human meningiomas. J Neurosurg 72:786791, 1990 Kazumoto K, Tamura M, Hoshino H, et al: Enhanced expression of the sis and c-myc oncogenes in human meningiomas. J Neurosurg 72:786–791, 1990

    • Search Google Scholar
    • Export Citation
  • 12.

    Kepes JJ: Meningiomas. Biology, Pathology and Differential Diagnosis. New York: Masson, 1982 Kepes JJ: Meningiomas. Biology, Pathology and Differential Diagnosis. New York: Masson, 1982

    • Search Google Scholar
    • Export Citation
  • 13.

    Kruijer W, , Cooper JA, & Hunter T, et al. : Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature 312:711716, 1985 Kruijer W, Cooper JA, Hunter T, et al: Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature 312:711–716, 1985

    • Search Google Scholar
    • Export Citation
  • 14.

    Lesch KP, , Engl HG, & Gross S: Androgen receptor binding activity in meningiomas. Surg Neurol 28:176180, 1987 Lesch KP, Engl HG, Gross S: Androgen receptor binding activity in meningiomas. Surg Neurol 28:176–180, 1987

    • Search Google Scholar
    • Export Citation
  • 15.

    Lesch KP, & Gross S: Estrogen receptor immunoreactivity in meningiomas. Comparison with the binding activity of estrogen, progesterone, and androgen receptors. J Neurosurg 67:237243, 1987 Lesch KP, Gross S: Estrogen receptor immunoreactivity in meningiomas. Comparison with the binding activity of estrogen, progesterone, and androgen receptors. J Neurosurg 67:237–243, 1987

    • Search Google Scholar
    • Export Citation
  • 16.

    Markwalder TM, , Gerber HA, & Waelti E, et al. : Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67. Surg Neurol 30:97101, 1988 Markwalder TM, Gerber HA, Waelti E, et al: Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67. Surg Neurol 30:97–101, 1988

    • Search Google Scholar
    • Export Citation
  • 17.

    Maxwell M, & Black PML: Oncogenes, growth factors and brain tumors, in Kornblith P, & Walker M (eds): Advances in Neurooncology. New York: Futura, 1988, pp 159176 Maxwell M, Black PML: Oncogenes, growth factors and brain tumors, in Kornblith P, Walker M (eds): Advances in Neurooncology. New York: Futura, 1988, pp 159–176

    • Search Google Scholar
    • Export Citation
  • 18.

    Maxwell M, , Galanopoulos T, & Hedley-Whyte ET, et al. : Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46:1621, 1990 Maxwell M, Galanopoulos T, Hedley-Whyte ET, et al: Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46:16–21, 1990

    • Search Google Scholar
    • Export Citation
  • 19.

    Maxwell M, , Naber SP, & Wolfe HJ, et al. : Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance. J Clin Invest 86:131140, 1990 Maxwell M, Naber SP, Wolfe HJ, et al: Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance. J Clin Invest 86:131–140, 1990

    • Search Google Scholar
    • Export Citation
  • 20.

    Smidt M, , Kirsch I, & Ratner L: Deletion of Alu sequences in the fifth c-sis intron in individuals with meningioma. J Clin Invest 86:11511157, 1990 Smidt M, Kirsch I, Ratner L: Deletion of Alu sequences in the fifth c-sis intron in individuals with meningioma. J Clin Invest 86:1151–1157, 1990

    • Search Google Scholar
    • Export Citation
  • 21.

    Wang JL, , Nistér M, & Hermansson M, et al. : Expression of PDGF β-receptors in human meningioma cells. Int J Cancer 46:772778, 1990 Wang JL, Nistér M, Hermansson M, et al: Expression of PDGF β-receptors in human meningioma cells. Int J Cancer 46:772–778, 1990

    • Search Google Scholar
    • Export Citation
  • 22.

    Weisman AS, , Raguet SS, & Kelly PA: Characterization of the epidermal growth factor receptor in human meningioma. Cancer Res 47:21722176, 1987 Weisman AS, Raguet SS, Kelly PA: Characterization of the epidermal growth factor receptor in human meningioma. Cancer Res 47:2172–2176, 1987

    • Search Google Scholar
    • Export Citation
  • 23.

    Westermark B, , Siegbahn A, & Heldin CH, et al. : β-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase. Proc Natl Acad Sci USA 87:128132, 1990 Westermark B, Siegbahn A, Heldin CH, et al: β-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase. Proc Natl Acad Sci USA 87:128–132, 1990

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 383 125 12
Full Text Views 145 2 0
PDF Downloads 74 2 0
EPUB Downloads 0 0 0