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Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo: clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues

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Abstract

In order to clarify the role of fibronectin in glioma invasion in vivo, we analyzed the relationship between fibronectin-stimulated cell migration and adhesion in 14 primary glioma cells and the expression of fibronectin and the fibronectin receptor in the corresponding tumor tissues. The tumors comprised nine glioblastomas (GB) and five anaplastic gliomas (AG) consisting of two astrocytomas, two oligoastrocytomas and one ependymoma. All glioma cells tested in the primary cell culture were found to migrate to fibronectin in a dose-dependent manner. The extent of cell migration to fibronectin was not significantly different for the GB and AG groups. On the other hand, cell adhesion to fibronectin in the AG was much stronger than that in the GB group. Immunohistochemistry demonstrated that fibronectin positively stained in the extra-cellular matrix (ECM) in eight cases and that the fibronectin receptor was positive in tumor cell membranes in 10 cases. In addition, cellular fibronectin isoforms containing ED-A and ED-B sequences were found to be immunolocalized in the tumor cells and the ECM of GB. These isoforms were also specifically expressed in tumor vessels within tumor tissues, but not in those within normal brain tissues. Cell migration tended to be expressed more strongly by glioma cells derived from tumor tissues in which fibronectin was posi-tively immunolocalized in the ECM than from tissues with negative fibronectin in the ECM. Four glioma cells derived from GB whose tumor cells did not positively stain for fibronectin receptors migrated much less extensively to fibronectin than other glioma cells whose tissues showed positive staining for the fibronectin receptor. Of these four GB, two had loss of heterozygosity in the locus of fibronectin receptor b1 gene. These results suggest that fibronectin deposited in the extracellular matrix of tumors, which can be derived from both plasma and the tumor cell itself, strongly promotes the migration of glioma cells, and that expression of the fibronectin receptor may play a critical role in the biological behavior of the tumor cells, particularly in fibronectin-stimulated cell migration in vivo.© Kluwer Academic Publishers 1998

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References

  1. Liotta LA, Rao CN and Wewer UM, 1986, Biochemical interactions of tumor cells with the basement membrane. Ann Rev Biochem, 55, 1037-57.

    Google Scholar 

  2. Mareel MM, 1980, Recent aspects of tumor invasiveness. In: Richter GW, Epstein MA, eds. International Review of Experimental Pathology. New York: Academic Press, 65-129.

    Google Scholar 

  3. Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Pearson CA and Sakakura T, 1986, Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell, 47, 131-9.

    Google Scholar 

  4. Reichardt LF and Tomaselli KJ, 1991, Extracellular matrix molecules and thier receptors: functions in neural development. Ann Rev Neurosci, 14, 531-70.

    Google Scholar 

  5. Sanes JR, 1989, Extracellular matrix molecules that influence neural developement. Ann Rev Neurosci, 12, 491-516.

    Google Scholar 

  6. Paetau A, Mellstrom K, Vaheri A and Haltia M, 1980, Distribution of a major connective tissue protein, fibronectin, in normal and neoplastic human nervous tissue. Acta Neuropathol, 51, 47-51.

    Google Scholar 

  7. Rutka JT, Apodaca G, Stern R and Rosenblum M, 1988, The extracellular matrix of the central and peripheral nervous systems: structure and function. J Neurosurg, 69, 155-70.

    Google Scholar 

  8. Carbonetto S, 1984, The extracellular matrix of the nervous system. Trends Neurosci, 7, 382-7.

    Google Scholar 

  9. Venstrom KA and Reichard LF, 1993, Extracellular matrix 2: role of extracellular matrix molecules and their receptors in the nervous system. FASEB, 7, 996-1003.

    Google Scholar 

  10. Schachner M, Schoonmaker G and Hynes RO, 1978, Cellular and subcellular localization of LETS protein in the nervous system. Brain Res, 158, 149-58.

    Google Scholar 

  11. Chintala SK, Sawaya R, Gokaslan ZL, et al.1996, Immunohistochemical localization of extracellular matrix proteins in human glioma, both in vivoand in vitro. Cancer Lett, 101, 107-14.

    Google Scholar 

  12. Bronner-Fraser M, 1986, An antibody to a receptor for fibronectin and laminin perturbs cranial neural crest development. Dev Biol, 117, 528-36.

    Google Scholar 

  13. Ohnishi T, Arita N, Hayakawa T, et al.1990, Motility factor produced by malignant glioma cells: role in tumor invasion. J Neurosurg, 73, 881-8.

    Google Scholar 

  14. Terranova VP, Rohrbach DH and Martin GR, 1980, Role of laminin in the attachment of PAM212 (epithelial) cells to basement membrane collagen. Cell, 22, 719-26.

    Google Scholar 

  15. Giese A, Rief HD, Loo A and Berens ME, 1994, Determinants of human astrocytoma migration. Cancer Res, 54, 3897-904.

    Google Scholar 

  16. Tysnes BB, Larsen LF, Ness GO, et al.1996, Stimulation of glioma-cell migration by laminin and inhibition by anti-α3 and anti-β1 integrin antibodies. Int J Cancer, 67, 777-84.

    Google Scholar 

  17. Ohnishi T, Arita N, Hiraga S, et al.1997, Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity. Clin Exp Metastasis, 15, 538-46.

    Google Scholar 

  18. Kleihues P, Burger PC and Scheithauer BW, eds, 1993, Histolgical Typing of Tumours of the Central Nervous System, 2nd ed. Berlin: Springer-Verlag.

    Google Scholar 

  19. Hsu SM, Raine L and Fanger H, 1981, Use of avidinbiotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem, 29, 577-80.

    Google Scholar 

  20. Cavenee WK, Dryja TP, Philips RA, et al.1984, Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13. Am J Hum Genet, 36, 10-24.

    Google Scholar 

  21. Freiberg AP and Vogelstein B, 1984, A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem, 137, 266-7.

    Google Scholar 

  22. Gutman A and Kornblihtt AR, 1987, Identification of a third region of cell-specific alternative splicing in human fibronectin mRNA. Proc Natl Acad Sci USA, 84, 7179-82.

    Google Scholar 

  23. Kornblihtt AR, Vibe-Pedersen K and Baralle FE, 1984, Human fibronectin: cell specific alternative mRNA splicing generates polypeptide chains differing in the number of internal repeats. Nucleic Acids Res, 12, 5853-68.

    Google Scholar 

  24. Schwarzbauer JE, Tamkun JW, Lemischka IR and Hynes RO, 1983, Three different fibronectin mRNAs arise by alternative splicing within the coding region. Cell, 35, 421-31.

    Google Scholar 

  25. Zardi L, Carnemolla B, Siri A, et al.1987, Transformed human cells produce a new fibronectin isoform by preferential alternative splicing of a previusly unobserved exon. EMBO J, 6, 2337-42.

    Google Scholar 

  26. Oyama F, Hirohashi S, Shimosato Y, et al.1990, Oncodevelopmental regulation of the alternative splicing of fibronectin pre-messenger RNA in human lung tissues. Cancer Res, 50, 1075-8.

    Google Scholar 

  27. Oyama F, Hirohashi S, Sakamoto M, et al.1993, Coorinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at EDA, ED-B, and CS1 regions in human liver tumors. Cancer Res, 33, 2005-11.

    Google Scholar 

  28. Friedlander DR, Zagzag D, Shiff B, et al.1996, Migration of brain tumor cells on extracellular matrix proteins in vitrocorrelates with tumor type and grade and involves av and b1 integrins. Cancer Res, 56, 1939-47.

    Google Scholar 

  29. Xia P and Culp LA, 1994, Adhesion activity in fibronectin’s alternatively spliced domain Eda (EIIIA) and its neighboring type III repeats: oncogene-dependent regulation. Exp Cell Res, 213, 253-65.

    Google Scholar 

  30. Chen W and Culp LA, 1996, Adhesion mediated by fibronectin’s alternatively spliced Edb (EIIIB) and its neighboring type III repeats. Exp Cell Res, 223, 9-19.

    Google Scholar 

  31. Hynes RO, 1987, Integrins: a family of cell surface receptors. Cell, 48, 549-54.

    Google Scholar 

  32. Hynes RO, 1992, Integrins: versatility, modulation, and signaling in cell adhesion. Cell, 69, 11-25.

    Google Scholar 

  33. Dedhar S and Saulnier R, 1990, Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. J Cell Biol, 110, 481-9.

    Google Scholar 

  34. Plantefaber LC and Hynes RO, 1989, Changes in integrin receptors on oncogenically transformed cells. Cell, 56, 281-90.

    Google Scholar 

  35. Singer II, Scott S, Kawka DW, et al.1988, Cell surface distribution of fibronectin and vitronectin receptors depends on substrate composition and extracellular matrix accumulation. J Cell Biol, 106, 2171-82.

    Google Scholar 

  36. Wayner EA, Garcia-Pardo A, Humphries MJ, et al.1989, Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol, 109, 1321-30.

    Google Scholar 

  37. Zhang Y, Saison M, Spaepen M, et al.1988, Mapping of human fibronectin receptor b subunit gene to chromosome 10. Somatic Cell Mol Genet, 14, 99-104.

    Google Scholar 

  38. Goodfellow PJ, Nevanlinna HA, Gorman P, et al.1989, Assignment of the gene encoding the beta subunit of the human fibronectin receptor (beta-FNR) to chromosome 10 p11.2. Ann Hum Genet, 53, 15-22.

    Google Scholar 

  39. Wu J, Giuffra LA, Goodfellow PJ, et al.1989, The β subunit locus of the human fibronectin receptor: DNA restriction fragment length polymorphism and linkage mapping studies. Hum Genet, 83, 383-90.

    Google Scholar 

  40. Shapiro WR, Hiesiger EM, Cooney GA, et al.1990, Temporal effects of dexamethasone on blood-to-brain and blood-to-tumor transport of 14C-alpha-aminoisobutyric acid in rat C6 glioma. J Neuro-Oncol, 8, 197-204.

    Google Scholar 

  41. Yamada K, Ushio Y, Hayakawa T, et al.1983, Effects of methyl-predonosolone on peritumoral brain edema. A quantitative autoradiographic study. J Neurosurg, 59, 612-9.

    Google Scholar 

  42. Enam SA, Rosenblum ML and Edvardsen K, 1998, Role of extracellular matrix in tumor invasion: migration of glioma cells along fibronectin-positive mesenchymal cell processes. Neurosurg, 42, 599-608.

    Google Scholar 

  43. Nakagawa T, Kubota T, Kabuto M, et al.1994, Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg, 81, 69-77.

    Google Scholar 

  44. Yamamoto M, Mohanam S, Sawaya R, et al.1996, Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivoand in vitro. Cancer Res, 56, 384-92.

    Google Scholar 

  45. Ohnishi T, Matsumura H, Izumoto S, et al.1998, A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res 58, 2935-40.

    Google Scholar 

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  1. Department of Neurosurgery, Osaka University Medical School, Suita, Osaka, Japan

    Takanori Ohnishi, Shoju Hiraga, Shuichi Izumoto, Hirotaka Matsumura, Yonehiro Kanemura, Norio Arita & Toru Hayakawa

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  1. Takanori Ohnishi
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  2. Shoju Hiraga
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  3. Shuichi Izumoto
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Ohnishi, T., Hiraga, S., Izumoto, S. et al. Role of fibronectin-stimulated tumor cell migration in glioma invasion in vivo: clinical significance of fibronectin and fibronectin receptor expressed in human glioma tissues. Clin Exp Metastasis 16, 729–741 (1998). https://doi.org/10.1023/A:1006532812408

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