This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hermanson, M. Articles by Nistér, M. Search for Related Content PubMed PubMed Citation Articles by Hermanson, M. Articles by Nistér, M.

Platelet-derived Growth Factor and Its Receptors in Human Glioma Tissue: Expression of Messenger RNA and Protein Suggests the Presence of Autocrine and Paracrine Loops¹

Ludwig Institute for Cancer Research, Biomedical Center S-751 23 [M. He., K. F., L. C-W., C-H. H.], and Department for Pathology, University Hospital, University of Uppsala, S-751 85 [M. Ha., B. W., M. N.], Uppsala, Sweden

The expression of platelet-derived growth factor (PDGF) and its receptors was analyzed in 14 gliomas of various degrees of malignancy and compared with three gliosis cases by in situ hybridization and immunohistochemistry techniques. Expression of both PDGF A- and B-chains was higher in glioblastomas than in astrocytomas. The PDGF A-chain mRNA was predominantly found in cell-rich areas in glioblastomas. The cognate PDGF- receptor (PDGFR-) mRNA was heterogeneously distributed in gliomas of all grades, and PDGFR- expression was higher in gliomas than in gliosis. Within some glioblastomas probed with PDGFR- complementary RNA, cells heavily loaded with grains were intermingled with others containing low or moderate signals. The heavily labeled cells were often found in the vicinity of proliferating capillaries. Immunostaining with an anti-PDGF antibody and an affinity-purified antiserum against the PDGFR- showed strong staining of most tumor cells with both antibodies in glioblastoma. In addition, the PDGFR- antibodies yielded a strong staining of scattered cells, and the anti-PDGF antibody yielded staining of a few cells within the astrocytoma. Furthermore, high levels of the PDGF-ß receptor (PDGFR-ß) and PDGF B-chain mRNA as well as the ß receptor protein were found in hyperplastic capillaries. These results suggest the presence of autocrine and paracrine loops in glioma, activating the PDGFR- in glioma cells and the PDGFR-ß in endothelial cells.

¹ Supported in part by grants from the Swedish Cancer Society and the Swedish Society of Medicine.

² To whom requests for reprints should be addressed.

Received 2/26/92. Accepted 3/25/92.

This article has been cited by other articles:

				S. Ning, J. A. Nemeth, R. L. Hanson, K. Forsythe, and S. J. Knox Anti-integrin monoclonal antibody CNTO 95 enhances the therapeutic efficacy of fractionated radiation therapy in vivo Mol. Cancer Ther., June 1, 2008; 7(6): 1569 - 1578. [Abstract] [Full Text] [PDF]

				J. Andrae, R. Gallini, and C. Betsholtz Role of platelet-derived growth factors in physiology and medicine Genes & Dev., May 15, 2008; 22(10): 1276 - 1312. [Abstract] [Full Text] [PDF]

				L. M. Petti, E. C. Ricciardi, H. J. Page, and K. A. Porter Transforming signals resulting from sustained activation of the PDGF{beta} receptor in mortal human fibroblasts J. Cell Sci., April 15, 2008; 121(8): 1172 - 1182. [Abstract] [Full Text] [PDF]

				O. J. Becher, D. Hambardzumyan, E. I. Fomchenko, H. Momota, L. Mainwaring, A.-M. Bleau, A. M. Katz, M. Edgar, A. M. Kenney, C. Cordon-Cardo, et al. Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor-Induced Gliomas Cancer Res., April 1, 2008; 68(7): 2241 - 2249. [Abstract] [Full Text] [PDF]

				D. S. Ziegler, A. L. Kung, and M. W. Kieran Anti-Apoptosis Mechanisms in Malignant Gliomas J. Clin. Oncol., January 20, 2008; 26(3): 493 - 500. [Abstract] [Full Text] [PDF]

				D. A. Reardon, A. Desjardins, J. J. Vredenburgh, S. Sathornsumetee, J. N. Rich, J. A. Quinn, T. F. Lagattuta, M. J. Egorin, S. Gururangan, R. McLendon, et al. Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: Phase 1 trial in adults with malignant glioma Neuro-oncol, January 1, 2008; 10(3): 330 - 340. [Abstract] [Full Text] [PDF]

				F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment Genes & Dev., November 1, 2007; 21(21): 2683 - 2710. [Abstract] [Full Text] [PDF]

				S. de Bouard, P. Herlin, J. G. Christensen, E. Lemoisson, P. Gauduchon, E. Raymond, and J.-S. Guillamo Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma Neuro-oncol, October 1, 2007; 9(4): 412 - 423. [Abstract] [Full Text] [PDF]

				M. Ferletta, L. Uhrbom, T. Olofsson, F. Ponten, and B. Westermark Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B Induced Gliomagenesis Mol. Cancer Res., September 1, 2007; 5(9): 891 - 897. [Abstract] [Full Text] [PDF]

				I. F. Pollack, R. I. Jakacki, S. M. Blaney, M. L. Hancock, M. W. Kieran, P. Phillips, L. E. Kun, H. Friedman, R. Packer, A. Banerjee, et al. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report Neuro-oncol, April 1, 2007; 9(2): 145 - 160. [Abstract] [Full Text] [PDF]

				M. Failly, S. Korur, V. Egler, J.-L. Boulay, M. M. Lino, R. Imber, and A. Merlo Combination of sublethal concentrations of epidermal growth factor receptor inhibitor and microtubule stabilizer induces apoptosis of glioblastoma cells Mol. Cancer Ther., February 1, 2007; 6(2): 773 - 781. [Abstract] [Full Text] [PDF]

				D. Matei, M. Satpathy, L. Cao, Y.-C. Lai, H. Nakshatri, and D. B. Donner The Platelet-derived Growth Factor Receptor {alpha} Is Destabilized by Geldanamycins in Cancer Cells J. Biol. Chem., January 5, 2007; 282(1): 445 - 453. [Abstract] [Full Text] [PDF]

				J. Baranowska-Kortylewicz, M. Abe, J. Nearman, and C. A. Enke Emerging Role of Platelet-Derived Growth Factor Receptor-{beta} Inhibition in Radioimmunotherapy of Experimental Pancreatic Cancer Clin. Cancer Res., January 1, 2007; 13(1): 299 - 306. [Abstract] [Full Text] [PDF]

				P. Y. Wen, W.K. A. Yung, K. R. Lamborn, P. L. Dahia, Y. Wang, B. Peng, L. E. Abrey, J. Raizer, T. F. Cloughesy, K. Fink, et al. Phase I/II Study of Imatinib Mesylate for Recurrent Malignant Gliomas: North American Brain Tumor Consortium Study 99-08. Clin. Cancer Res., August 15, 2006; 12(16): 4899 - 4907. [Abstract] [Full Text] [PDF]

				M. Assanah, R. Lochhead, A. Ogden, J. Bruce, J. Goldman, and P. Canoll Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J. Neurosci., June 21, 2006; 26(25): 6781 - 6790. [Abstract] [Full Text] [PDF]

				D. A. Reardon, J. N. Rich, H. S. Friedman, and D. D. Bigner Recent Advances in the Treatment of Malignant Astrocytoma J. Clin. Oncol., March 10, 2006; 24(8): 1253 - 1265. [Abstract] [Full Text] [PDF]

				D. A. Reardon, J. A. Quinn, J. J. Vredenburgh, S. Gururangan, A. H. Friedman, A. Desjardins, S. Sathornsumetee, J. E. Herndon II, J. M. Dowell, R. E. McLendon, et al. Phase 1 Trial of Gefitinib Plus Sirolimus in Adults with Recurrent Malignant Glioma Clin. Cancer Res., February 1, 2006; 12(3): 860 - 868. [Abstract] [Full Text] [PDF]

				D. A. Reardon, M. J. Egorin, J. A. Quinn, J. N. Rich Sr, I. Gururangan, J. J. Vredenburgh, A. Desjardins, S. Sathornsumetee, J. M. Provenzale, J. E. Herndon II, et al. Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme J. Clin. Oncol., December 20, 2005; 23(36): 9359 - 9368. [Abstract] [Full Text] [PDF]

				B. M. Woerner, N. M. Warrington, A. L. Kung, A. Perry, and J. B. Rubin Widespread CXCR4 Activation in Astrocytomas Revealed by Phospho-CXCR4-Specific Antibodies Cancer Res., December 15, 2005; 65(24): 11392 - 11399. [Abstract] [Full Text] [PDF]

				G. Dresemann Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series Ann. Onc., October 1, 2005; 16(10): 1702 - 1708. [Abstract] [Full Text] [PDF]

				S. P. Fraser, J. K.J. Diss, A.-M. Chioni, M. E. Mycielska, H. Pan, R. F. Yamaci, F. Pani, Z. Siwy, M. Krasowska, Z. Grzywna, et al. Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis Clin. Cancer Res., August 1, 2005; 11(15): 5381 - 5389. [Abstract] [Full Text] [PDF]

				D. S. Krause and R. A. Van Etten Tyrosine Kinases as Targets for Cancer Therapy N. Engl. J. Med., July 14, 2005; 353(2): 172 - 187. [Full Text] [PDF]

				D. Ma, C. L. Nutt, P. Shanehsaz, X. Peng, D. N. Louis, and D. M. Kaetzel Autocrine Platelet-Derived Growth Factor-Dependent Gene Expression in Glioblastoma Cells Is Mediated Largely by Activation of the Transcription Factor Sterol Regulatory Element Binding Protein and Is Associated with Altered Genotype and Patient Survival in Human Brain Tumors Cancer Res., July 1, 2005; 65(13): 5523 - 5534. [Abstract] [Full Text] [PDF]

				M. R. Stettner, W. Wang, L. B. Nabors, S. Bharara, D. C. Flynn, J. R. Grammer, G. Y. Gillespie, and C. L. Gladson Lyn Kinase Activity Is the Predominant Cellular Src Kinase Activity in Glioblastoma Tumor Cells Cancer Res., July 1, 2005; 65(13): 5535 - 5543. [Abstract] [Full Text] [PDF]

				N. Loizos, Y. Xu, J. Huber, M. Liu, D. Lu, B. Finnerty, R. Rolser, A. Malikzay, A. Persaud, E. Corcoran, et al. Targeting the platelet-derived growth factor receptor {alpha} with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: Implications as a potential therapeutic target Mol. Cancer Ther., March 1, 2005; 4(3): 369 - 379. [Abstract] [Full Text] [PDF]

				W. G. Roberts, P. M. Whalen, E. Soderstrom, G. Moraski, J. P. Lyssikatos, H.-F. Wang, B. Cooper, D. A. Baker, D. Savage, D. Dalvie, et al. Antiangiogenic and Antitumor Activity of a Selective PDGFR Tyrosine Kinase Inhibitor, CP-673,451 Cancer Res., February 1, 2005; 65(3): 957 - 966. [Abstract] [Full Text] [PDF]

				C De Bustos, A Smits, B Stromberg, V P Collins, M Nister, and G Afink A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas J. Med. Genet., January 1, 2005; 42(1): 31 - 37. [Abstract] [Full Text] [PDF]

				A. H. Shih, C. Dai, X. Hu, M. K. Rosenblum, J. A. Koutcher, and E. C. Holland Dose-Dependent Effects of Platelet-Derived Growth Factor-B on Glial Tumorigenesis Cancer Res., July 15, 2004; 64(14): 4783 - 4789. [Abstract] [Full Text] [PDF]

				M. Furuhashi, T. Sjoblom, A. Abramsson, J. Ellingsen, P. Micke, H. Li, E. Bergsten-Folestad, U. Eriksson, R. Heuchel, C. Betsholtz, et al. Platelet-Derived Growth Factor Production by B16 Melanoma Cells Leads to Increased Pericyte Abundance in Tumors and an Associated Increase in Tumor Growth Rate Cancer Res., April 15, 2004; 64(8): 2725 - 2733. [Abstract] [Full Text] [PDF]

				R. V. Hoch and P. Soriano Roles of PDGF in animal development Development, October 15, 2003; 130(20): 4769 - 4784. [Abstract] [Full Text] [PDF]

				Q. Ding, J. Stewart Jr., M. A. Olman, M. R. Klobe, and C. L. Gladson The Pattern of Enhancement of Src Kinase Activity on Platelet-derived Growth Factor Stimulation of Glioblastoma Cells Is Affected by the Integrin Engaged J. Biol. Chem., October 10, 2003; 278(41): 39882 - 39891. [Abstract] [Full Text] [PDF]

				G. Hesselager, L. Uhrbom, B. Westermark, and M. Nister Complementary Effects of Platelet-derived Growth Factor Autocrine Stimulation and p53 or Ink4a-Arf Deletion in a Mouse Glioma Model Cancer Res., August 1, 2003; 63(15): 4305 - 4309. [Abstract] [Full Text] [PDF]

				P. Guo, B. Hu, W. Gu, L. Xu, D. Wang, H.-J. S. Huang, W. K. Cavenee, and S.-Y. Cheng Platelet-Derived Growth Factor-B Enhances Glioma Angiogenesis by Stimulating Vascular Endothelial Growth Factor Expression in Tumor Endothelia and by Promoting Pericyte Recruitment Am. J. Pathol., April 1, 2003; 162(4): 1083 - 1093. [Abstract] [Full Text] [PDF]

				H. Uehara, S. J. Kim, T. Karashima, D. L. Shepherd, D. Fan, R. Tsan, J. J. Killion, C. Logothetis, P. Mathew, and I. J. Fidler Effects of Blocking Platelet-Derived Growth Factor-Receptor Signaling in a Mouse Model of Experimental Prostate Cancer Bone Metastases J Natl Cancer Inst, March 19, 2003; 95(6): 458 - 470. [Abstract] [Full Text] [PDF]

				J. M.L. Ebos, J. Tran, Z. Master, D. Dumont, J. V. Melo, E. Buchdunger, and R. S. Kerbel Imatinib Mesylate (STI-571) Reduces Bcr-Abl-Mediated Vascular Endothelial Growth Factor Secretion in Chronic Myelogenous Leukemia Mol. Cancer Res., December 1, 2002; 1(2): 89 - 95. [Abstract] [Full Text] [PDF]

				N. A. Lokker, C. M. Sullivan, S. J. Hollenbach, M. A. Israel, and N. A. Giese Platelet-derived Growth Factor (PDGF) Autocrine Signaling Regulates Survival and Mitogenic Pathways in Glioblastoma Cells: Evidence That the Novel PDGF-C and PDGF-D Ligands May Play a Role in the Development of Brain Tumors Cancer Res., July 1, 2002; 62(13): 3729 - 3735. [Abstract] [Full Text] [PDF]

				D Ribom, J Andrae, M Frielingsdorf, M Hartman, M Nister, and A Smits Prognostic value of platelet derived growth factor {alpha} receptor expression in grade 2 astrocytomas and oligoastrocytomas J. Neurol. Neurosurg. Psychiatry, June 1, 2002; 72(6): 782 - 787. [Abstract] [Full Text] [PDF]

				C.S. Brock and S.M. Lee Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer Eur. Respir. J., March 1, 2002; 19(3): 557 - 570. [Abstract] [Full Text] [PDF]

				J.-C. Yu, N. A. Lokker, S. Hollenbach, M. Apatira, J. Li, A. Betz, D. Sedlock, S. Oda, Y. Nomoto, K. Matsuno, et al. Efficacy of the Novel Selective Platelet-Derived Growth Factor Receptor Antagonist CT52923 on Cellular Proliferation, Migration, and Suppression of Neointima following Vascular Injury J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1172 - 1178. [Abstract] [Full Text] [PDF]

				C. Dai, J. C. Celestino, Y. Okada, D. N. Louis, G. N. Fuller, and E. C. Holland PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo Genes & Dev., August 1, 2001; 15(15): 1913 - 1925. [Abstract] [Full Text] [PDF]

				E. A. Maher, F. B. Furnari, R. M. Bachoo, D. H. Rowitch, D. N. Louis, W. K. Cavenee, and R. A. DePinho Malignant glioma: genetics and biology of a grave matter Genes & Dev., June 1, 2001; 15(11): 1311 - 1333. [Full Text] [PDF]

				H. Huang, S. Colella, M. Kurrer, Y. Yonekawa, P. Kleihues, and H. Ohgaki Gene Expression Profiling of Low-Grade Diffuse Astrocytomas by cDNA Arrays Cancer Res., December 1, 2000; 60(24): 6868 - 6874. [Abstract] [Full Text]

				E. Buchdunger, C. L. Cioffi, N. Law, D. Stover, S. Ohno-Jones, B. J. Druker, and N. B. Lydon Abl Protein-Tyrosine Kinase Inhibitor STI571 Inhibits In Vitro Signal Transduction Mediated by c-Kit and Platelet-Derived Growth Factor Receptors J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 139 - 145. [Abstract] [Full Text]

				T. Kilic, J. A. Alberta, P. R. Zdunek, M. Acar, P. Iannarelli, T. O’Reilly, E. Buchdunger, P. M. Black, and C. D. Stiles Intracranial Inhibition of Platelet-derived Growth Factor-mediated Glioblastoma Cell Growth by an Orally Active Kinase Inhibitor of the 2-Phenylaminopyrimidine Class Cancer Res., September 1, 2000; 60(18): 5143 - 5150. [Abstract] [Full Text]

				L. M. Strawn, F. Kabbinavar, D. P. Schwartz, E. Mann, L. K. Shawver, D. J. Slamon, and J. M. Cherrington Effects of SU101 in Combination with Cytotoxic Agents on the Growth of Subcutaneous Tumor Xenografts Clin. Cancer Res., July 1, 2000; 6(7): 2931 - 2940. [Abstract] [Full Text]

				C.-H. Heldin and B. Westermark Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor Physiol Rev, October 1, 1999; 79(4): 1283 - 1316. [Abstract] [Full Text] [PDF]

				Y. Shoshan, A. Nishiyama, A. Chang, S. Mork, G. H. Barnett, J. K. Cowell, B. D. Trapp, and S. M. Staugaitis Expression of oligodendrocyte progenitor cell antigens by gliomas: Implications for the histogenesis of brain tumors PNAS, August 31, 1999; 96(18): 10361 - 10366. [Abstract] [Full Text] [PDF]

				S. G. Eckhardt, J. Rizzo, K. R. Sweeney, G. Cropp, S. D. Baker, J. G. Kuhn, M. A. Villalona-Calero, L. Hammond, G. Weiss, A. Thurman, et al. Phase I and Pharmacologic Study of the Tyrosine Kinase Inhibitor SU101 in Patients With Advanced Solid Tumors J. Clin. Oncol., April 1, 1999; 17(4): 1095 - 1095. [Abstract] [Full Text] [PDF]

				D. Wang, H-J. S. Huang, A. Kazlauskas, and W. K. Cavenee Induction of Vascular Endothelial Growth Factor Expression in Endothelial Cells by Platelet-derived Growth Factor through the Activation of Phosphatidylinositol 3-Kinase Cancer Res., April 1, 1999; 59(7): 1464 - 1472. [Abstract] [Full Text] [PDF]

				O. Bögler, M. Nagane, J. Gillis, H-J. Su Huang, and W. K. Cavenee Malignant Transformation of p53-deficient Astrocytes Is Modulated by Environmental Cues in Vitro Cell Growth Differ., February 1, 1999; 10(2): 73 - 86. [Abstract] [Full Text]

				M. C. Coffey, J. E. Strong, P. A. Forsyth, and P. W. Lee Reovirus Therapy of Tumors with Activated Ras Pathway Science, November 13, 1998; 282(5392): 1332 - 1334. [Abstract] [Full Text]

				S. Sultana, R. Zhou, M. S. Sadagopan, and O. Skalli Effects of Growth Factors and Basement Membrane Proteins on the Phenotype of U-373 MG Glioblastoma Cells as Determined by the Expression of Intermediate Filament Proteins Am. J. Pathol., October 1, 1998; 153(4): 1157 - 1168. [Abstract] [Full Text] [PDF]

				J. A. Epstein, B. Song, M. Lakkis, and C. Wang Tumor-Specific PAX3-FKHR Transcription Factor, but Not PAX3, Activates the Platelet-Derived Growth Factor Alpha Receptor Mol. Cell. Biol., July 1, 1998; 18(7): 4118 - 4130. [Abstract] [Full Text]

				D. M. O'Rourke, X. Qian, H.-T. Zhang, J. G. Davis, E. Nute, J. Meinkoth, and M. I. Greene Trans receptor inhibition of human glioblastoma cells by erbB family ectodomains PNAS, April 1, 1997; 94(7): 3250 - 3255. [Abstract] [Full Text] [PDF]

				J. Krupinski, R. Issa, T. Bujny, M. Slevin, P. Kumar, S. Kumar, and J. Kaluza A Putative Role for Platelet-Derived Growth Factor in Angiogenesis and Neuroprotection After Ischemic Stroke in Humans Stroke, March 1, 1997; 28(3): 564 - 573. [Abstract] [Full Text]

				S. Valgeirsdóttir, A. Eriksson, M. Nistér, C.-H. Heldin, B. Westermark, and L. Claesson-Welsh Compartmentalization of Autocrine Signal Transduction Pathways in Sis-transformed NIH 3T3 Cells J. Biol. Chem., April 28, 1995; 270(17): 10161 - 10170. [Abstract] [Full Text] [PDF]