Journal of Neuro-Oncology

, Volume 3, Issue 2, pp 181–186 | Cite as

Immunolocalization of monoclonal antibody-defined extracellular matrix antigens in human brain tumors

  • Rodney D. McComb
  • Darell D. Bigner
Article

Summary

The extracellular matrix is involved in many aspects of tumor cell biology, including tumor invasion and metastasis. 2A6 and 81C6 are murine monoclonal antibodies that identify glioma-mesenchymal extracellular matrix antigens. The 81C6 antigen is a high molecular weight glycoprotein composed of Mr 230,000 subunits. The expression of 2A6 antigen, 81C6 glycoprotein, fibronectin (FN), and laminin (LN) was examined immunohistochemically in ten malignant gliomas (MG) and four medulloblastomas (MBT). 2A6 and 81C6 were expressed in similar patterns by the neoplastic neuroepithelial cells in 9/10 MG and 1/4 MBT. The staining was typically diffuse and amorphous, without visualization of distinct cell bodies or processes. Less frequently, antigen was detected within tumor cell cytoplasm. In most tumors the staining was greatest in the perivascular regions. In two MG, 2A6 and 81 C6 were expressed only by a subpopulation of neoplastic cells. Although intense staining was also associated with hyperplastic vascular and mesenchymal cells, many small and medium size blood vessels stained weakly or not at all. In contrast, FN and LN were expressed uniformly and intensely in the tumor vasculature, but were not expressed by neoplastic neuroepithelial cells. The 2A6 antigen and 81C6 glycoprotein are immunohistochemically distinct from FN and LN. These monoclonal antibody-defined antigens are heterogeneously expressed by neoplastic neuroepithelial cells and hyperplastic vascular-mesenchymal elements in MG and MBT. The 2A6 and 81C6 monoclonal antibodies will be useful reagents in the investigation of the extracellular matrix of malignant neuroepithelial neoplasms.

Key words

extracellular matrix monoclonal antibody fibronectin laminin brain neoplasm invasion 

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References

  1. 1.
    Liotta LA, Rao CN, Barsky SH: Tumor invasion and the extracellular matrix. Lab Invest 49:636–649, 1983.PubMedGoogle Scholar
  2. 2.
    Pauli BU, Schwartz DE, Thonar EJM, Kuettner KE: Tumor invasion and host extracellular matrix. Cancer Metastasis Rev 2:129–152, 1983.PubMedGoogle Scholar
  3. 3.
    Paetau A, Mellstrom K, Vaheri A, Haltia M: Distribution of a major connective tissue protein, fibronectin, in normal and neoplastic human nervous tissue. Acta Neuropathol (Berl) 51:47–51, 1980.Google Scholar
  4. 4.
    Jones TR, Ruoslahti E, Schold SC, Bigner DD: Fibronectin and glial fibrillary acidic protein expression in normal human brain and anaplastic human gliomas. Cancer Res 42:168–177, 1982.PubMedGoogle Scholar
  5. 5.
    Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD: Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res 43:2796–2805, 1983.PubMedGoogle Scholar
  6. 6.
    Kochi N, Tani E, Morimura T, Itagaki T: Immunohistochemical study of fibronectin in human glioma and meningioma. Acta Neuropathol (Berl) 59:119–126, 1983.Google Scholar
  7. 7.
    Mauro A, Bertolotto A, Germano I, Giaccone G, Giordana MT, Migheli A, Schiffer D: Collagenase in the immunohistochemical demonstration of laminin, fibronectin and factor VIII/RAg in nervous tissue after fixation. Histochemistry 80:157–163, 1984.PubMedGoogle Scholar
  8. 8.
    McComb RD, Bigner DD: Immunolocalization of laminin in neoplasms of the central and peripheral nervous systems. J Neuropathol Exp Neurol 44: 242–253, 1985.PubMedGoogle Scholar
  9. 9.
    Glimelius B, Norling B, Westermark B, Wasteson A: Composition and distribution of glycosaminoglycans in cultures of human normal and malignant glial cells. Biochem J 172:443–456, 1978.PubMedGoogle Scholar
  10. 10.
    Alitalo K, Vaheri A: Pericellular matrix in malignant transformation. Adv Cancer Res 37:111–158, 1982.PubMedGoogle Scholar
  11. 11.
    Liotta LA: Tumor invasion and metastases: Role of the basement membrane. Am J Pathol 117:339–348, 1984.PubMedGoogle Scholar
  12. 12.
    McComb RD, Bourdon MA, Bigner DD: Extracellular matrix (ECM) antigen defined by a monoclonal antibody (MA) raised against the medulloblastoma-derived cell line TE-671: Comparison with the glioma-mesenchymal extracellular matrix (GMEM) antigen and fibronectin (FN) (Abstract). J Neuropathol Exp Neurol 43:336, 1984.Google Scholar
  13. 13.
    Pierschbacher MD, Hayman EG, Ruoslahti E: Location of the cell-attachment site in fibronectin with monoclonal antibodies and proteolytic fragments of the molecule. Cell 26:259–269, 1981.PubMedGoogle Scholar
  14. 14.
    Margulies DH, Kuehl WM, Scharff MD: Somatic cell hybridization of mouse myeloma cells. Cell 8:405–415, 1976.PubMedGoogle Scholar
  15. 15.
    Wewer U, Albrechtsen R, Manthorpe M, Varon S, Engvall E, Ruoslahti E: Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis. J Biol Chem 258:12654–12660, 1983.PubMedGoogle Scholar
  16. 16.
    Hsu SM, Raine L, Fanger H: Use of avid in-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580, 1981PubMedGoogle Scholar
  17. 17.
    Bourdon MA, Matthews TJ, Pizzo SV, Bigner DD: Immunochemical and biochemical characterization of a glioma-associated extracellular matrix glycoprotein. Cell Biochem, in press, 1985.Google Scholar
  18. 18.
    Schiffer D, Giordana MT, Mauro A, Migheli A: GFAP, FVIII/Rag, laminin, and fibronectin in gliosarcomas: An immunohistochemical study. Acta Neuropathol (Berl) 63:108–116, 1984.Google Scholar
  19. 19.
    Bigner DD, Bigner SH, Ponten J, Westermark B, Mahaley Jr MS, Ruoslathi E, Herschman H, Eng LF, Wikstrand CJ: Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 40:201–229, 1981.PubMedGoogle Scholar
  20. 20.
    Alitalo K, Bornstein P, Vaheri A, Sage H: Biosynthesis of an unusual collagen type by human astrocytoma cells in vitro. J Biol Chem 258:2653–2661, 1983.PubMedGoogle Scholar
  21. 21.
    Kavinsky CJ, Garber BB: Fibronectin associated with the glial component of embryonic brain cell cultures. J Supramol Struct 11:269–281, 1979.PubMedGoogle Scholar
  22. 22.
    Liesi P, Dahl D, Vaheri A: Laminin is produced by early rat astrocytes in primary culture. J Cell Biol 96:920–924, 1983.PubMedGoogle Scholar
  23. 23.
    McComb RD, Bigner DD: The biology of malignant gliomas: A comprehensive survey. Clin Neuropathol 3:93–106, 1984.PubMedGoogle Scholar
  24. 24.
    Engelhardt A: Detection of acid mucopolysaccharides in human brain tumors by histochemical methods. Acta Neuropathol (Berl) 49:199–203, 1980.Google Scholar
  25. 25.
    Scherer HJ: Structural development in gliomas. Am J Cancer 34:333–351, 1938.Google Scholar
  26. 26.
    Singh M, Bachhawat BK: Isolation and characterization of glycosaminoglycans in human brain of different age groups. J Neurochem 15:249–258, 1968.Google Scholar
  27. 27.
    Dorfman A, Ho PL: Synthesis of acid mucopolysaccharides by glial tumor cells in tissue culture. Proc Natl Acad Sci USA 66:495–499, 1970.PubMedGoogle Scholar
  28. 28.
    Smith B, Butler M: Acid mucopolysaccharides in tumors of the myelin sheath cells, the oligodendrogliomas and the neurilemmoma. Acta Neuropathol (Berl) 23:181–185, 1973.Google Scholar
  29. 29.
    Toole BP: Glycosaminoglycans in morphogenesis. In: ED Hay (ed) Cell biology of extracellular matrix. Plenum Press, New York, 1982, pp.259–294.Google Scholar
  30. 30.
    Toole BP, Biswas C, Gross J: Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci USA 76:6299–6303, 1979.PubMedGoogle Scholar
  31. 31.
    Rollins BJ, Culp LA: Glycosaminoglycans in the substrate adhesion sites of normal and virus-transformed murine cells. Biochem 18:141–148, 1979.Google Scholar
  32. 32.
    Culp LA, Murray BA, Rollins BJ: Fibronectin and proteoglycans as determinants of cell-substratum adhesion. J Supramol Struct 11:401–427, 1979PubMedGoogle Scholar
  33. 33.
    Margolis RU, Margolis RK: Metabolism and function of glycoproteins and glycosaminoglycans in nervous tissue. Int J Biochem 8:85–91, 1977.Google Scholar
  34. 34.
    Delpech B, Halavent C: Characterization and purification from human brain of a hyaluronic acid-binding glycoprotein, hyaluronectin. J Neurochem 36:855–859, 1981.PubMedGoogle Scholar
  35. 35.
    Girard N, Tayot J, Delpech B, Delpech A, Clement JC, Creissard P, Laumonier R: Brain glycoprotein in tumours of the nervous system. J Neuropathol Exp Neurol 39:88–98, 1980.PubMedGoogle Scholar
  36. 36.
    Delpech B, Delpech A, Girard N, Chauzy C, Laumonier R: An antigen associated with mesenchyme in human tumours that cross-reacts with brain glycoprotein. Br J Cancer 40:123–133, 1979.PubMedGoogle Scholar
  37. 37.
    Hynes RO, Yamada KM: Fibronectins: Multifunctional modular glycoproteins. J Cell Biol 95:369–377, 1982.PubMedGoogle Scholar
  38. 38.
    Bourdon MA, Coleman RE, Blasberg RG, Groothuis DR, Bigner DD: Monoclonal antibody localization in subcutaneous and intracranial human glioma xenografts: Paired-label and imaging analysis. Anticancer Res 4:133–140, 1984.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers 1985

Authors and Affiliations

  • Rodney D. McComb
    • 1
  • Darell D. Bigner
    • 2
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Nebraska Medical CenterOmaha
  2. 2.Department of PathologyDuke University Medical CenterDurham

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