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. 1993 Jul;143(1):154–163.

Characterization of integrin receptors in normal and neoplastic human brain.

W Paulus 1, I Baur 1, D Schuppan 1, W Roggendorf 1
PMCID: PMC1886949  PMID: 8317546

Abstract

We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiyama H., Kawamata T., Dedhar S., McGeer P. L. Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue. J Neuroimmunol. 1991 Apr;32(1):19–28. doi: 10.1016/0165-5728(91)90067-h. [DOI] [PubMed] [Google Scholar]
  2. Akiyama H., McGeer P. L. Brain microglia constitutively express beta-2 integrins. J Neuroimmunol. 1990 Nov;30(1):81–93. doi: 10.1016/0165-5728(90)90055-r. [DOI] [PubMed] [Google Scholar]
  3. Albelda S. M., Mette S. A., Elder D. E., Stewart R., Damjanovich L., Herlyn M., Buck C. A. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990 Oct 15;50(20):6757–6764. [PubMed] [Google Scholar]
  4. Bednarczyk J. L., McIntyre B. W. Expression and ligand-binding function of the integrin alpha 4 beta 1 (VLA-4) on neural-crest-derived tumor cell lines. Clin Exp Metastasis. 1992 Jul;10(4):281–290. doi: 10.1007/BF00133564. [DOI] [PubMed] [Google Scholar]
  5. Bellon G., Caulet T., Cam Y., Pluot M., Poulin G., Pytlinska M., Bernard M. H. Immunohistochemical localisation of macromolecules of the basement membrane and extracellular matrix of human gliomas and meningiomas. Acta Neuropathol. 1985;66(3):245–252. doi: 10.1007/BF00688590. [DOI] [PubMed] [Google Scholar]
  6. Bjerkvig R., Laerum O. D., Rucklidge G. J. Immunocytochemical characterization of extracellular matrix proteins expressed by cultured glioma cells. Cancer Res. 1989 Oct 1;49(19):5424–5428. [PubMed] [Google Scholar]
  7. Bronner-Fraser M. An antibody to a receptor for fibronectin and laminin perturbs cranial neural crest development in vivo. Dev Biol. 1986 Oct;117(2):528–536. doi: 10.1016/0012-1606(86)90320-9. [DOI] [PubMed] [Google Scholar]
  8. Chan B. M., Matsuura N., Takada Y., Zetter B. R., Hemler M. E. In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science. 1991 Mar 29;251(5001):1600–1602. doi: 10.1126/science.2011740. [DOI] [PubMed] [Google Scholar]
  9. Couldwell W. T., de Tribolet N., Antel J. P., Gauthier T., Kuppner M. C. Adhesion molecules and malignant gliomas: implications for tumorigenesis. J Neurosurg. 1992 May;76(5):782–791. doi: 10.3171/jns.1992.76.5.0782. [DOI] [PubMed] [Google Scholar]
  10. Dedhar S., Robertson K., Gray V. Induction of expression of the alpha v beta 1 and alpha v beta 3 integrin heterodimers during retinoic acid-induced neuronal differentiation of murine embryonal carcinoma cells. J Biol Chem. 1991 Nov 15;266(32):21846–21852. [PubMed] [Google Scholar]
  11. Dedhar S., Saulnier R. Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. J Cell Biol. 1990 Feb;110(2):481–489. doi: 10.1083/jcb.110.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Erickson H. P., Bourdon M. A. Tenascin: an extracellular matrix protein prominent in specialized embryonic tissues and tumors. Annu Rev Cell Biol. 1989;5:71–92. doi: 10.1146/annurev.cb.05.110189.000443. [DOI] [PubMed] [Google Scholar]
  13. Gehlsen K. R., Davis G. E., Sriramarao P. Integrin expression in human melanoma cells with differing invasive and metastatic properties. Clin Exp Metastasis. 1992 Mar;10(2):111–120. doi: 10.1007/BF00114587. [DOI] [PubMed] [Google Scholar]
  14. Gehlsen K. R., Dillner L., Engvall E., Ruoslahti E. The human laminin receptor is a member of the integrin family of cell adhesion receptors. Science. 1988 Sep 2;241(4870):1228–1229. doi: 10.1126/science.2970671. [DOI] [PubMed] [Google Scholar]
  15. Ghahary A., Bhatnagar R., Price K., Forsyth N. L., Shen Y. J., Tredget T. E., Malhotra S. K. Rat glioma cell lines C6 and 9L synthesize type 1 collagen in vitro. Brain Res Bull. 1992 Jan;28(1):47–56. doi: 10.1016/0361-9230(92)90229-q. [DOI] [PubMed] [Google Scholar]
  16. Gladson C. L., Cheresh D. A. Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest. 1991 Dec;88(6):1924–1932. doi: 10.1172/JCI115516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hildreth J. E., Gotch F. M., Hildreth P. D., McMichael A. J. A human lymphocyte-associated antigen involved in cell-mediated lympholysis. Eur J Immunol. 1983 Mar;13(3):202–208. doi: 10.1002/eji.1830130305. [DOI] [PubMed] [Google Scholar]
  18. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  19. Kakita A., Wakabayashi K., Takahashi H., Ohama E., Ikuta F., Tokiguchi S. Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies. Acta Neuropathol. 1992;83(5):538–542. doi: 10.1007/BF00310033. [DOI] [PubMed] [Google Scholar]
  20. Keizer G. D., Borst J., Figdor C. G., Spits H., Miedema F., Terhorst C., De Vries J. E. Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. Eur J Immunol. 1985 Nov;15(11):1142–1148. doi: 10.1002/eji.1830151114. [DOI] [PubMed] [Google Scholar]
  21. Kennel S. J., Foote L. J., Falcioni R., Sonnenberg A., Stringer C. D., Crouse C., Hemler M. E. Analysis of the tumor-associated antigen TSP-180. Identity with alpha 6-beta 4 in the integrin superfamily. J Biol Chem. 1989 Sep 15;264(26):15515–15521. [PubMed] [Google Scholar]
  22. Kennel S. J., Godfrey V., Ch'ang L. Y., Lankford T. K., Foote L. J., Makkinje A. The beta 4 subunit of the integrin family is displayed on a restricted subset of endothelium in mice. J Cell Sci. 1992 Jan;101(Pt 1):145–150. doi: 10.1242/jcs.101.1.145. [DOI] [PubMed] [Google Scholar]
  23. Lauweryns B., van den Oord J. J., Volpes R., Foets B., Missotten L. Distribution of very late activation integrins in the human cornea. An immunohistochemical study using monoclonal antibodies. Invest Ophthalmol Vis Sci. 1991 Jun;32(7):2079–2085. [PubMed] [Google Scholar]
  24. Lein P. J., Higgins D., Turner D. C., Flier L. A., Terranova V. P. The NC1 domain of type IV collagen promotes axonal growth in sympathetic neurons through interaction with the alpha 1 beta 1 integrin. J Cell Biol. 1991 Apr;113(2):417–428. doi: 10.1083/jcb.113.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Liesi P., Kaakkola S., Dahl D., Vaheri A. Laminin is induced in astrocytes of adult brain by injury. EMBO J. 1984 Mar;3(3):683–686. doi: 10.1002/j.1460-2075.1984.tb01867.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Malek-Hedayat S., Rome L. H. Expression of multiple integrins and extracellular matrix components by C6 glioma cells. J Neurosci Res. 1992 Mar;31(3):470–478. doi: 10.1002/jnr.490310309. [DOI] [PubMed] [Google Scholar]
  27. Mariani Costantini R., Falcioni R., Battista P., Zupi G., Kennel S. J., Colasante A., Venturo I., Curio C. G., Sacchi A. Integrin (alpha 6/beta 4) expression in human lung cancer as monitored by specific monoclonal antibodies. Cancer Res. 1990 Sep 15;50(18):6107–6112. [PubMed] [Google Scholar]
  28. McComb R. D., Bigner D. D. Immunolocalization of monoclonal antibody-defined extracellular matrix antigens in human brain tumors. J Neurooncol. 1985;3(2):181–186. doi: 10.1007/BF02228895. [DOI] [PubMed] [Google Scholar]
  29. McGeer P. L., Zhu S. G., Dedhar S. Immunostaining of human brain capillaries by antibodies to very late antigens. J Neuroimmunol. 1990 Mar;26(3):213–218. doi: 10.1016/0165-5728(90)90003-6. [DOI] [PubMed] [Google Scholar]
  30. McKeever P. E., Davenport R. D., Shakui P. Patterns of antigenic expression of human glioma cells. Crit Rev Neurobiol. 1991;6(2):119–147. [PubMed] [Google Scholar]
  31. Morimura T., Neuchrist C., Kitz K., Budka H., Scheiner O., Kraft D., Lassmann H. Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol. 1990;80(3):287–294. doi: 10.1007/BF00294647. [DOI] [PubMed] [Google Scholar]
  32. Natali P. G., Nicotra M. R., Cavaliere R., Giannarelli D., Bigotti A. Tumor progression in human malignant melanoma is associated with changes in alpha 6/beta 1 laminin receptor. Int J Cancer. 1991 Sep 9;49(2):168–172. doi: 10.1002/ijc.2910490203. [DOI] [PubMed] [Google Scholar]
  33. Paulus W., Roggendorf W., Schuppan D. Immunohistochemical investigation of collagen subtypes in human glioblastomas. Virchows Arch A Pathol Anat Histopathol. 1988;413(4):325–332. doi: 10.1007/BF00783025. [DOI] [PubMed] [Google Scholar]
  34. Pignatelli M., Smith M. E., Bodmer W. F. Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br J Cancer. 1990 Apr;61(4):636–638. doi: 10.1038/bjc.1990.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Reichardt L. F., Tomaselli K. J. Extracellular matrix molecules and their receptors: functions in neural development. Annu Rev Neurosci. 1991;14:531–570. doi: 10.1146/annurev.ne.14.030191.002531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ruan C. G. [Monoclonal antibody SZ-21 to platelet membrane glycoprotein IIIa]. Zhonghua Yi Xue Za Zhi. 1987 Feb;67(2):76–78. [PubMed] [Google Scholar]
  37. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rutka J. T., Apodaca G., Stern R., Rosenblum M. The extracellular matrix of the central and peripheral nervous systems: structure and function. J Neurosurg. 1988 Aug;69(2):155–170. doi: 10.3171/jns.1988.69.2.0155. [DOI] [PubMed] [Google Scholar]
  39. Rutka J. T., Giblin J. R., Apodaca G., DeArmond S. J., Stern R., Rosenblum M. L. Inhibition of growth and induction of differentiation in a malignant human glioma cell line by normal leptomeningeal extracellular matrix proteins. Cancer Res. 1987 Jul 1;47(13):3515–3522. [PubMed] [Google Scholar]
  40. Schuppan D., Cantaluppi M. C., Becker J., Veit A., Bunte T., Troyer D., Schuppan F., Schmid M., Ackermann R., Hahn E. G. Undulin, an extracellular matrix glycoprotein associated with collagen fibrils. J Biol Chem. 1990 May 25;265(15):8823–8832. [PubMed] [Google Scholar]
  41. Schuppan D., Rühlmann T., Hahn E. G. Radioimmunoassay for human type VI collagen and its application to tissue and body fluids. Anal Biochem. 1985 Aug 15;149(1):238–247. doi: 10.1016/0003-2697(85)90501-9. [DOI] [PubMed] [Google Scholar]
  42. Schwarting R., Stein H., Wang C. Y. The monoclonal antibodies alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) allow the diagnosis of hairy cell leukemia. Blood. 1985 Apr;65(4):974–983. [PubMed] [Google Scholar]
  43. Song W. K., Wang W., Foster R. F., Bielser D. A., Kaufman S. J. H36-alpha 7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis. J Cell Biol. 1992 May;117(3):643–657. doi: 10.1083/jcb.117.3.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sonnenberg A., Janssen H., Hogervorst F., Calafat J., Hilgers J. A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody. J Biol Chem. 1987 Jul 25;262(21):10376–10383. [PubMed] [Google Scholar]
  45. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  46. Stamp G. W., Pignatelli M. Distribution of beta 1, alpha 1, alpha 2 and alpha 3 integrin chains in basal cell carcinomas. J Pathol. 1991 Apr;163(4):307–313. doi: 10.1002/path.1711630407. [DOI] [PubMed] [Google Scholar]
  47. Tomaselli K. J., Hall D. E., Flier L. A., Gehlsen K. R., Turner D. C., Carbonetto S., Reichardt L. F. A neuronal cell line (PC12) expresses two beta 1-class integrins-alpha 1 beta 1 and alpha 3 beta 1-that recognize different neurite outgrowth-promoting domains in laminin. Neuron. 1990 Nov;5(5):651–662. doi: 10.1016/0896-6273(90)90219-6. [DOI] [PubMed] [Google Scholar]
  48. Tuszynski G. P., Kowalska M. A. Thrombospondin-induced adhesion of human platelets. J Clin Invest. 1991 Apr;87(4):1387–1394. doi: 10.1172/JCI115144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Virtanen I., Korhonen M., Kariniemi A. L., Gould V. E., Laitinen L., Ylänne J. Integrins in human cells and tumors. Cell Differ Dev. 1990 Dec 2;32(3):215–227. doi: 10.1016/0922-3371(90)90034-t. [DOI] [PubMed] [Google Scholar]
  50. Wayner E. A., Carter W. G., Piotrowicz R. S., Kunicki T. J. The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa. J Cell Biol. 1988 Nov;107(5):1881–1891. doi: 10.1083/jcb.107.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wayner E. A., Garcia-Pardo A., Humphries M. J., McDonald J. A., Carter W. G. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol. 1989 Sep;109(3):1321–1330. doi: 10.1083/jcb.109.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zutter M. M. Immunolocalization of integrin receptors in normal lymphoid tissues. Blood. 1991 May 15;77(10):2231–2236. [PubMed] [Google Scholar]
  54. Zutter M. M., Mazoujian G., Santoro S. A. Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. Am J Pathol. 1990 Oct;137(4):863–870. [PMC free article] [PubMed] [Google Scholar]
  55. Zutter M. M., Santoro S. A. Widespread histologic distribution of the alpha 2 beta 1 integrin cell-surface collagen receptor. Am J Pathol. 1990 Jul;137(1):113–120. [PMC free article] [PubMed] [Google Scholar]
  56. de Vries J. E., Keizer G. D., te Velde A. A., Voordouw A., Ruiter D., Rümke P., Spits H., Figdor C. G. Characterization of melanoma-associated surface antigens involved in the adhesion and motility of human melanoma cells. Int J Cancer. 1986 Oct 15;38(4):465–473. doi: 10.1002/ijc.2910380403. [DOI] [PubMed] [Google Scholar]
  57. von der Mark H., Dürr J., Sonnenberg A., von der Mark K., Deutzmann R., Goodman S. L. Skeletal myoblasts utilize a novel beta 1-series integrin and not alpha 6 beta 1 for binding to the E8 and T8 fragments of laminin. J Biol Chem. 1991 Dec 15;266(35):23593–23601. [PubMed] [Google Scholar]

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