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. 1996 Feb;148(2):367–373.

Ezrin expression in stromal cells of capillary hemangioblastoma. An immunohistochemical survey of brain tumors.

T Böhling 1, O Turunen 1, J Jääskeläinen 1, O Carpen 1, M Sainio 1, T Wahlström 1, A Vaheri 1, M Haltia 1
PMCID: PMC1861673  PMID: 8579099

Abstract

Ezrin is a cytoskeleton-associated protein that appears to link actin filaments to the plasma membrane. Immunocytochemical studies suggest that ezrin is expressed in epithelial cells but not in mesenchymal cells. In addition, ezrin is expressed by certain epithelial tumors, such as renal cell adenocarcinomas. Ezrin serves as a tyrosine kinase substrate, and is phosphorylated in epidermal growth factor-stimulated cells. Ezrin may thus mediate regulatory signals in different cell functions. We studied the distribution of ezrin in 104 cases of primary tumors of the central nervous system (CNS) by immunocytochemistry. Special interest was focused on capillary hemangioblastoma, owing to its resemblance to renal cell adenocarcinoma, and on malignant gliomas, owing to their frequent epidermal growth factor receptor amplification. The stromal cells of hemangioblastomas were found to be strongly positive for ezrin. No expression was detected in gliomas and, except for hemangioblastomas, ezrin expression was restricted to those few CNS tumors that show epithelial differentiation, ie, choroid plexus papillomas, craniopharyngiomas, ependymomas, and cysts. The diffuse cytoplasmic expression of ezrin in the stromal cells of capillary hemangioblastoma may indicate that stromal cells overexpress ezrin or express ezrin with deficient binding properties.

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Selected References

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  1. Algrain M., Turunen O., Vaheri A., Louvard D., Arpin M. Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker. J Cell Biol. 1993 Jan;120(1):129–139. doi: 10.1083/jcb.120.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arpin M., Algrain M., Louvard D. Membrane-actin microfilament connections: an increasing diversity of players related to band 4.1. Curr Opin Cell Biol. 1994 Feb;6(1):136–141. doi: 10.1016/0955-0674(94)90127-9. [DOI] [PubMed] [Google Scholar]
  3. Berryman M., Franck Z., Bretscher A. Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J Cell Sci. 1993 Aug;105(Pt 4):1025–1043. doi: 10.1242/jcs.105.4.1025. [DOI] [PubMed] [Google Scholar]
  4. Birgbauer E., Dinsmore J. H., Winckler B., Lander A. D., Solomon F. Association of ezrin isoforms with the neuronal cytoskeleton. J Neurosci Res. 1991 Sep;30(1):232–241. doi: 10.1002/jnr.490300124. [DOI] [PubMed] [Google Scholar]
  5. Bretscher A. Purification of an 80,000-dalton protein that is a component of the isolated microvillus cytoskeleton, and its localization in nonmuscle cells. J Cell Biol. 1983 Aug;97(2):425–432. doi: 10.1083/jcb.97.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bretscher A. Rapid phosphorylation and reorganization of ezrin and spectrin accompany morphological changes induced in A-431 cells by epidermal growth factor. J Cell Biol. 1989 Mar;108(3):921–930. doi: 10.1083/jcb.108.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collins V. P. Amplified genes in human gliomas. Semin Cancer Biol. 1993 Feb;4(1):27–32. [PubMed] [Google Scholar]
  8. Crossey P. A., Foster K., Richards F. M., Phipps M. E., Latif F., Tory K., Jones M. H., Bentley E., Kumar R., Lerman M. I. Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours. Hum Genet. 1994 Jan;93(1):53–58. doi: 10.1007/BF00218913. [DOI] [PubMed] [Google Scholar]
  9. Edwards K. A., Montague R. A., Shepard S., Edgar B. A., Erikson R. L., Kiehart D. P. Identification of Drosophila cytoskeletal proteins by induction of abnormal cell shape in fission yeast. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4589–4593. doi: 10.1073/pnas.91.10.4589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Everett A. W., Nichol K. A. Ezrin immunoreactivity in neuron subpopulations: cellular distribution in relation to cytoskeletal proteins in sensory neurons. J Histochem Cytochem. 1990 Aug;38(8):1137–1144. doi: 10.1177/38.8.2114439. [DOI] [PubMed] [Google Scholar]
  11. Frank T. S., Trojanowski J. Q., Roberts S. A., Brooks J. J. A detailed immunohistochemical analysis of cerebellar hemangioblastoma: an undifferentiated mesenchymal tumor. Mod Pathol. 1989 Nov;2(6):638–651. [PubMed] [Google Scholar]
  12. Gould K. L., Bretscher A., Esch F. S., Hunter T. cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. EMBO J. 1989 Dec 20;8(13):4133–4142. doi: 10.1002/j.1460-2075.1989.tb08598.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hansen K., Møller J. V. Application of two-dimensional gel analysis to identification and characterization of tyrosine phosphorylated substrates for growth factor receptors. Electrophoresis. 1993 Jan-Feb;14(1-2):112–126. doi: 10.1002/elps.1150140120. [DOI] [PubMed] [Google Scholar]
  14. Hanzel D., Reggio H., Bretscher A., Forte J. G., Mangeat P. The secretion-stimulated 80K phosphoprotein of parietal cells is ezrin, and has properties of a membrane cytoskeletal linker in the induced apical microvilli. EMBO J. 1991 Sep;10(9):2363–2373. doi: 10.1002/j.1460-2075.1991.tb07775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hufnagel T. J., Kim J. H., True L. D., Manuelidis E. E. Immunohistochemistry of capillary hemangioblastoma. Immunoperoxidase-labeled antibody staining resolves the differential diagnosis with metastatic renal cell carcinoma, but does not explain the histogenesis of the capillary hemangioblastoma. Am J Surg Pathol. 1989 Mar;13(3):207–216. [PubMed] [Google Scholar]
  16. Janmey P. A., Chaponnier C. Medical aspects of the actin cytoskeleton. Curr Opin Cell Biol. 1995 Feb;7(1):111–117. doi: 10.1016/0955-0674(95)80052-2. [DOI] [PubMed] [Google Scholar]
  17. Jooss K. U., Müller R. Deregulation of genes encoding microfilament-associated proteins during Fos-induced morphological transformation. Oncogene. 1995 Feb 2;10(3):603–608. [PubMed] [Google Scholar]
  18. Jurco S., 3rd, Nadji M., Harvey D. G., Parker J. C., Jr, Font R. L., Morales A. R. Hemangioblastomas: histogenesis of the stromal cell studied by immunocytochemistry. Hum Pathol. 1982 Jan;13(1):13–18. doi: 10.1016/s0046-8177(82)80133-0. [DOI] [PubMed] [Google Scholar]
  19. Krieg J., Hunter T. Identification of the two major epidermal growth factor-induced tyrosine phosphorylation sites in the microvillar core protein ezrin. J Biol Chem. 1992 Sep 25;267(27):19258–19265. [PubMed] [Google Scholar]
  20. Lankes W. T., Furthmayr H. Moesin: a member of the protein 4.1-talin-ezrin family of proteins. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8297–8301. doi: 10.1073/pnas.88.19.8297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Latif F., Tory K., Gnarra J., Yao M., Duh F. M., Orcutt M. L., Stackhouse T., Kuzmin I., Modi W., Geil L. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317–1320. doi: 10.1126/science.8493574. [DOI] [PubMed] [Google Scholar]
  22. Luna E. J. Molecular links between the cytoskeleton and membranes. Curr Opin Cell Biol. 1991 Feb;3(1):120–126. doi: 10.1016/0955-0674(91)90174-w. [DOI] [PubMed] [Google Scholar]
  23. Maher E. R., Yates J. R., Harries R., Benjamin C., Harris R., Moore A. T., Ferguson-Smith M. A. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990 Nov;77(283):1151–1163. doi: 10.1093/qjmed/77.2.1151. [DOI] [PubMed] [Google Scholar]
  24. Martin M., Andréoli C., Sahuquet A., Montcourrier P., Algrain M., Mangeat P. Ezrin NH2-terminal domain inhibits the cell extension activity of the COOH-terminal domain. J Cell Biol. 1995 Mar;128(6):1081–1093. doi: 10.1083/jcb.128.6.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neumann H. P., Eggert H. R., Scheremet R., Schumacher M., Mohadjer M., Wakhloo A. K., Volk B., Hettmannsperger U., Riegler P., Schollmeyer P. Central nervous system lesions in von Hippel-Lindau syndrome. J Neurol Neurosurg Psychiatry. 1992 Oct;55(10):898–901. doi: 10.1136/jnnp.55.10.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Neumann H. P., Lips C. J., Hsia Y. E., Zbar B. Von Hippel-Lindau syndrome. Brain Pathol. 1995 Apr;5(2):181–193. doi: 10.1111/j.1750-3639.1995.tb00592.x. [DOI] [PubMed] [Google Scholar]
  27. Pakkanen R., Hedman K., Turunen O., Wahlström T., Vaheri A. Microvillus-specific Mr 75,000 plasma membrane protein of human choriocarcinoma cells. J Histochem Cytochem. 1987 Aug;35(8):809–816. doi: 10.1177/35.8.3298422. [DOI] [PubMed] [Google Scholar]
  28. Pakkanen R. Immunofluorescent and immunochemical evidence for the expression of cytovillin in the microvilli of a wide range of cultured human cells. J Cell Biochem. 1988 Sep;38(1):65–75. doi: 10.1002/jcb.240380107. [DOI] [PubMed] [Google Scholar]
  29. Rao P. H., Murty V. V., Gaidano G., Hauptschein R., Dalla-Favera R., Chaganti R. S. Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;66(4):272–273. doi: 10.1159/000133710. [DOI] [PubMed] [Google Scholar]
  30. Sato N., Funayama N., Nagafuchi A., Yonemura S., Tsukita S., Tsukita S. A gene family consisting of ezrin, radixin and moesin. Its specific localization at actin filament/plasma membrane association sites. J Cell Sci. 1992 Sep;103(Pt 1):131–143. doi: 10.1242/jcs.103.1.131. [DOI] [PubMed] [Google Scholar]
  31. Shuster C. B., Herman I. M. Indirect association of ezrin with F-actin: isoform specificity and calcium sensitivity. J Cell Biol. 1995 Mar;128(5):837–848. doi: 10.1083/jcb.128.5.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Suni J., Närvänen A., Wahlström T., Aho M., Pakkanen R., Vaheri A., Copeland T., Cohen M., Oroszlan S. Human placental syncytiotrophoblastic Mr 75,000 polypeptide defined by antibodies to a synthetic peptide based on a cloned human endogenous retroviral DNA sequence. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6197–6201. doi: 10.1073/pnas.81.19.6197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Takeuchi K., Sato N., Kasahara H., Funayama N., Nagafuchi A., Yonemura S., Tsukita S., Tsukita S. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. J Cell Biol. 1994 Jun;125(6):1371–1384. doi: 10.1083/jcb.125.6.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tanimura A., Nakamura Y., Hachisuka H., Tanimura Y., Fukumura A. Hemangioblastoma of the central nervous system: nature of the stromal cells as studied by the immunoperoxidase technique. Hum Pathol. 1984 Sep;15(9):866–869. doi: 10.1016/s0046-8177(84)80148-3. [DOI] [PubMed] [Google Scholar]
  35. Tikoo A., Varga M., Ramesh V., Gusella J., Maruta H. An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). J Biol Chem. 1994 Sep 23;269(38):23387–23390. [PubMed] [Google Scholar]
  36. Trofatter J. A., MacCollin M. M., Rutter J. L., Murrell J. R., Duyao M. P., Parry D. M., Eldridge R., Kley N., Menon A. G., Pulaski K. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Mar 12;72(5):791–800. doi: 10.1016/0092-8674(93)90406-g. [DOI] [PubMed] [Google Scholar]
  37. Tsukita S., Itoh M., Nagafuchi A., Yonemura S., Tsukita S. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J Cell Biol. 1993 Dec;123(5):1049–1053. doi: 10.1083/jcb.123.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tsukita S., Oishi K., Sato N., Sagara J., Kawai A., Tsukita S. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J Cell Biol. 1994 Jul;126(2):391–401. doi: 10.1083/jcb.126.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Turunen O., Wahlström T., Vaheri A. Ezrin has a COOH-terminal actin-binding site that is conserved in the ezrin protein family. J Cell Biol. 1994 Sep;126(6):1445–1453. doi: 10.1083/jcb.126.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Turunen O., Winqvist R., Pakkanen R., Grzeschik K. H., Wahlström T., Vaheri A. Cytovillin, a microvillar Mr 75,000 protein. cDNA sequence, prokaryotic expression, and chromosomal localization. J Biol Chem. 1989 Oct 5;264(28):16727–16732. [PubMed] [Google Scholar]
  41. Wahlström T., Närvänen A., Suni J., Pakkanen R., Lehtonen T., Saksela E., Vaheri A., Copeland T., Cohen M., Oroszlan S. Mr 75,000 protein, a tumor marker in renal adenocarcinoma, reacting with antibodies to a synthetic peptide based on a cloned human endogenous retroviral nucleotide sequence. Int J Cancer. 1985 Sep 15;36(3):379–382. [PubMed] [Google Scholar]

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