Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator

Oncogene volume 21, pages 7824–7830 (2002)Cite this article

Abstract

The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on the surface of tumor cells is involved in the activation of proteolytic cascades responsible for the invasiveness of those cells. The diffuse, extensive infiltration of glioblastomas into the surrounding normal brain tissue is believed to rely on modifications of the proteolysis of extracellular matrix components; blocking the interaction between uPA and uPAR might be a suitable approach for inhibiting glioma tumorigenesis. We assessed how expression of an amino-terminal fragment (ATF) of uPA that contains binding site to uPAR affects the invasiveness of SNB19 human glioblastoma cells. SNB19 cells were transfected with an expression plasmid (pcDNA3-ATF) containing a cDNA sequence of ATF-uPA. The resulting ATF-uPA-expressing clones showed markedly less cell adhesion, spreading, and clonogenicity than did control cells. Endogenous ATF expression also significantly decreased the invasive capacity of transfected glioblastoma cells in Matrigel and spheroid-rat brain cell aggregate models. ATF-uPA transfectants were also markedly less invasive than parental SNB19 cells after injection into the brains of nude mice, suggesting that competitive inhibition of the uPA-uPAR interaction on SNB19 cells by means of transfection with ATF cDNA could be a useful therapeutic strategy for inhibiting tumor progression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Andreasen PA, Kjoller L, Christensen L, Duffy MJ . 1997 Int. J. Cancer 72: 1–22

  • Burgle M, Koppitz M, Riemer C, Kessler H, Konig B, Weidle UH, Kellermann J, Lottspeich F, Graeff H, Schmitt M, Goretzki L, Reuning U, Wilhelm O, Magdolen V . 1997 J. Biol. Chem. 378: 231–237

  • Crowley CW, Cohen RL, Lucas BK, Liu G, Shuman MA, Levinson AD . 1993 Proc. Natl. Acad. Sci. USA. 90: 5021–5025

  • Dear AE, Medcalf RL . 1998 Eur. J. Biochem. 252: 185–193

  • Duffy MJ . 1996 Clin. Cancer Res. 2: 613–618

  • Festuccia C, Dolo V, Guerra F, Violini S, Muzi P, Pavan A, Bologna M . 1998 Clin. Exp. Metastasis 16: 513–528

  • Go Y, Chintala SK, Mohanam S, Gokaslan Z, Venkaiah B, Bjerkvig R, Oka K, Nicolson GL, Sawaya R, Rao JS . 1997 Clin. Exp. Metastasis 15: 440–446

  • Kobayashi H, Gotoh J, Fujie M, Shinohara H, Moniwa N, Terao T . 1994 Int. J. Cancer 57: 727–733

  • Kruger A, Soeltl R, Lutz V, Wilhelm OG, Magdolen V, Rojo EE, Hantzopoulos PA, Graeff H, Gansbacher B, Schmitt M . 2000 Cancer Gene Ther. 7: 292–299

  • Li H, Lu H, Griscelli F, Opolon P, Sun LQ, Ragot T, Legrand Y, Belin D, Soria J, Soria C, Perricaudet M, Yeh P . 1998 Gene. Ther. 5: 1105–1113

  • Luparello C, Del Rosso M . 1996 Eur. J. Cancer 32A: 702–707

  • Min HY, Doyle LV, Vitt CR, Zandonella CL, Stratton-Thomas JR, Shuman MA, Rosenberg S . 1996 Cancer Res. 56: 2428–2433

  • Mohanam S, Chintala SK, Go Y, Bhattacharya A, Venkaiah B, Boyd D, Gokaslan ZL, Sawaya R, Rao JS . 1997 Oncogene 14: 1351–1359

  • Mohanam S, Jasti SL, Kondraganti SR, Chandrasekar N, Kin Y, Fuller GN, Lakka SS, Kyritsis AP, Dinh DH, Olivero WC, Gujrati M, Yung WK, Rao JS . 2001 Clin. Cancer Res. 7: 2519–2526

  • Mohanam S, Sawaya R, McCutcheon I, Ali-Osman F, Boyd D, Rao JS . 1993 Cancer Res. 53: 4143–4147

  • Quax PH, Grimbergen JM, Lansink M, Bakker AH, Blatter MC, Belin D, van Hinsbergh VW, Verheijen JH . 1998 Arterioscler. Thromb. Vasc. Biol. 18: 693–701

  • Quax PH, Lamfers ML, Lardenoye JH, Grimbergen JM, de Vries MR, Slomp J, de Ruiter MC, Kockx MM, Verheijen JH, van Hinsbergh VW . 2001 Circulation 103: 562–569

  • Rabbani SA, Mazar AP, Bernier SM, Haq M, Bolivar I, Henkin J, Goltzman D . 1992 J. Biol. Chem. 267: 14151–14156

  • Reuning U, Magdolen V, Wilhelm O, Fischer K, Lutz V, Graeff H, Schmitt M . 1998 Int. J. Oncol. 13: 893–906

  • Schmitt M, Wilhelm OG, Reuning U, Kruger A, Harbeck N, Lengyel E, Graeff H, Gansbacher B, Kessler H, Burgle M, Sturzebecher J, Sperl S, Magdolen V . 2000 Fibrinol. Proteol. 14: 114–132

  • Stahl A, Mueller BM . 1997 Int. J. Cancer 71: 116–122

  • Waltz DA, Fujita RM, Yang X, Natkin L, Zhuo S, Gerard CJ, Rosenberg S, Chapman HA . 2000 Am. J. Respir. Cell Mol. Biol. 22: 316–322

  • Yamamoto M, Sawaya R, Mohanam S, Bindal AK, Bruner JM, Oka K, Rao VH, Tomonaga M, Nicolson GL, Rao JS . 1994a Cancer Res. 54: 3656–3661

  • Yamamoto M, Sawaya R, Mohanam S, Rao VH, Bruner JM, Nicolson GL, Rao JS . 1994b Cancer Res. 54: 5016–5020

  • Zhu F, Jia S, Xing G, Gao L, Zhang L, He F . 2001 DNA Cell Biol. 20: 297–305

Download references

Acknowledgements

We thank Karen Minter for preparing the manuscript. This work was supported by National Cancer Institute grants CA76350, CA75557 and CA85216 (to JS Rao).

Author information

Authors and Affiliations

  1. Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA

    Sanjeeva Mohanam, Nirmala Chandrasekar, Niranjan Yanamandra, Faiz Mirza & Jasti S Rao

  2. Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA

    Siddique Khawar, Dzung H Dinh, William C Olivero & Jasti S Rao

Authors
  1. Sanjeeva Mohanam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nirmala Chandrasekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Niranjan Yanamandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siddique Khawar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Faiz Mirza
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dzung H Dinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. William C Olivero
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jasti S Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jasti S Rao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mohanam, S., Chandrasekar, N., Yanamandra, N. et al. Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator. Oncogene 21, 7824–7830 (2002). https://doi.org/10.1038/sj.onc.1205893

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205893

Keywords

This article is cited by

Search

Advanced search

Quick links