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:

A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion

Oncogene volume 20, pages 6938–6945 (2001)Cite this article

Abstract

Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase-type plasminogen activator, tissue plasminogen activator, or thrombin. Preliminary findings in our laboratory suggested that the expression of TFPI-2 is downregulated or lost during tumor progression in human gliomas. To investigate the role of TFPI-2 in the invasiveness of brain tumors, we stably transfected the human high-grade glioma cell line SNB19 and the human low-grade glioma cell line Hs683 with a vector capable of expressing a transcript complementary to the full-length TFPI-2 mRNA in either sense (0.7 kb) or antisense (1 kb) orientations. Parental cells and stably transfected cell lines were analysed for TFPI-2 protein by Western blotting and for TFPI-2 mRNA by Northern blotting. The levels of TFPI-2 protein and mRNA were higher in the sense clones (SNB19) and decreased in the antisense (Hs683) clones than in the corresponding parental and vector controls. In spheroid and matrigel invasion assays, the SNB19 parental cells were highly invasive, but the sense-transfected SNB-19 clones were much less invasive; the antisense-transfected Hs683 clones were more invasive than their parental and vector controls. After intracerebral injection in mice, the sense-transfected SNB19 clones were less able to form tumors than were their parental and vector controls, and the antisense-Hs683 clones but not the parental or vector controls formed small tumors. This is the first study to demonstrate that down- or upregulation of TFPI-2 plays a significant role in the invasive behavior of human gliomas.

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

Similar content being viewed by others

Abbreviations

ECM:

extracellular matrix

uPA:

urokinase-type plasminogen activator

uPAR:

uPA receptor

tPA:

tissue type plasminogen activator

PAI-1:

plasminogen activator inhibitor-1

PMA:

phorbol 12 myristate 13-acetate

mTFPI-2:

recombinant trypsin/tissue factor pathway inhibitor-2

References

  • Bizik J, Lizonova A, Stephens RW, Grofova M, Vaheri A . 1990 Cell Regulation 1: 895–905

  • Chomczynski P, Sacchi N . 1987 Anal. Biochem. 162: 156–159

  • Contrino J, Hair G, Kreutzer DL, Rickles FR . 1996 Nature Medicine 2: 209–215

  • Duffy MJ . 1992 Clin. Exp. Metast. 10: 145–155

  • Dvorak HF . 1987 Hum. Pathol. 18: 275–284

  • Ehrlich HJ, Gebbink RK, Preissner KT, Keijer J, Esmon NL, Mertens K, Pannekoek H . 1991 J. Cell. Biol. 115: 1773–1781

  • Eitzman DT, Krauss JC, Shen T, Cui J, Ginsburg D . 1996 Blood 87: 4718–4722

  • Gladson CL, Pijuan-Thompson V, Olman MA, Gillespie GY, Yacoub IZ . 1995 Am. J. Pathol. 146: 1150–1160

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

  • Hembrough TA, Ruiz JF, Papathanassiu AE, Green SJ, Strickland DK . 2001 J. Biol. Chem. 276: 12241–12248

  • Iino M, Foster DC, Kisiel W . 1998 Arterioscler. Thromb. Vasc. Biol. 18: 40–46

  • Kondraganti S, Mohanam S, Chintala SK, Kin Y, Jasti SL, Nirmala C, Lakka SS, Adachi Y, Kyritsis AP, Ali-Osman F, Sawaya R, Fuller GN, Rao JS . 2000 Cancer Res. 60: 6851–6855

  • Konduri SD, Anastasia T, Nirmala C, Rao JS . 2000 Clin. Exp. Metast. 18: 303–308

  • Konduri SD, Tasiou A, Chandrasekar N, Rao JS . 2001 Int. J. Oncol. 18: 127–131

  • Koshikawa N, Yasumitsu H, Nagashima Y, Umeda M, Miyazaki K . 1994 Biochem. J. 303: 187–190

  • Koshikawa N, Yasumitsu H, Umeda M, Miyazaki K . 1992 Cancer Res. 52: 5046–5053

  • Kramer MD, Reinartz J, Brunner G, Schirrmacher V . 1994 Invas. Metas. 14: 210–222

  • Kwaan HC . 1992 Cancer Metast. Rev. 11: 291–311

  • Laemmli UK . 1970 Nature 227: 680–685

  • Lakka SS, Konduri SD, Mohanam S, Nicolson GL, Rao JS . 2000 Clin. Exp. Metast. 18: 239–244

  • Lund-Johansen M, Bjerkvig R, Rucklidge GJ . 1990 Spheroid culture in cancer research Bjerkvig R (ed) CRC Press, Ann Arbor pp. 3–18

    Google Scholar 

  • Mignatti P, Rifkin DB . 1993 Physiol. Rev. 73: 161–195

  • Miyagi Y, Koshikawa N, Yasumitsu H, Miyagi E, Hirahara F, Aoki I, Misugi K, Umeda M, Miyazaki K . 1994a J. Biochem. 116: 939–942

  • Miyagi Y, Yasumitsu H, Mizushima H, Koshikawa N, Matsuda Y, Itoh H, Hori TA, Aoki I, Misugi K, Miyazaki K . 1996b DNA Cell. Biol. 15: 947–954

  • Miyazaki K, Hattori Y, Umenishi F, Yasumitsu H, Umeda M . 1990 Cancer Res. 50: 7758–7764

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

  • Mueller BM, Reisfeld RA, Edgington TS, Ruf W . 1992 Proc. Natl. Acad. Sci. USA 89: 11832–11836

  • Mueller BM, Ruf W . 1998 J. Clin. Invest. 101: 1372–1378

  • Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds JJ . 1992 Ann. N Y Acad. Sci. 667: 1–12

  • Nakagawa K, Zhang Y, Tsuji H, Yoshizumi M, Kasahara T, Nishimura H, Nawroth PP, Nakagawa M . 1998 Sem. Thromb. Hem. 24: 207–210

  • Neaud V, Hisaka T, Monvoisin A, Bedin C, Balabaud C, Foster DC, Desmouli, Kisiel W, Rosenbaum J . 2000 J. Biol. Chem. 275: 35565–35569

  • Ollivier V, Bentolila S, Chabbat J, Hakim J, de Prost D . 1998 Blood 91: 2698–2703

  • Pedersen PH, Marienhagen K, Mork S, Bjerkvig R . 1993 Cancer Res. 53: 5158–5165

  • Pemberton PA, Wong DT, Gibson HL, Kiefer MC, Fitzpatrick PA, Sager R, Barr PJ . 1995 J. Biol. Chem. 270: 15832–15837

  • Petersen LC, Sprecher CA, Foster DC, Blumberg H, Hamamoto T, Kisiel W . 1996 Biochemistry 35: 266–272

  • Quax PH, van Muijen GN, Weening-Verhoeff EJ, Lund LR, Dano K, Ruiter DJ, Verheijen JH . 1991 J. Cell. Biol. 115: 191–199

  • Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W, Woodley DT . 1998 Int. J. Cancer 76: 749–756

  • Rao CN, Gomez DE, Woodley DT, Thorgeirsson UP . 1995a Arch. Biochem. Biophys. 319: 55–62

  • Rao CN, Lakka SS, Kin Y, Konduri S, Fuller GN, Mohanam S, Ali-Osman F, Sawaya R, Rao JS . 2001 Clin. Cancer Res. 7: 570–576

  • Rao CN, Liu YY, Peavey CL, Woodley DT . 1995b Arch. Biochem. Biophys. 317: 311–314

  • Rao CN, Mohanam S, Puppala A, Rao JS . 1999 Biochem. Biophys. Res. Commun. 255: 94–98

  • Rao CN, Peavey CL, Liu YY, Lapiere JC, Woodley DT . 1995c J. Invest. Dermatol. 104: 379–383

  • Rao CN, Reddy P, Liu Y, O'Toole E, Reeder D, Foster DC, Kisiel W, Woodley DT . 1996 Arch. Biochem. Biophys. 335: 82–92

  • Reinartz J, Batrla R, Boukamp P, Fusenig N, Kramer MD . 1993 Exp. Cell. Res. 208: 197–208

  • Ruf W, Mueller BM . 1996 Curr. Opin. Hematol. 3: 379–384

  • Seftor RE, Seftor EA, Sheng S, Pemberton PA, Sager R, Hendrix MJ . 1998 Cancer Res. 58: 5681–5685

  • Sheng S, Truong B, Fredrickson D, Wu R, Pardee AB, Sager R . 1998 Proc. Natl. Acad. Sci. USA 95: 499–504

  • Shoji M, Hancock WW, Abe K, Micko C, Casper KA, Baine RM, Wilcox JN, Danave I, Dillehay DL, Matthews E, Contrino J, Morrissey JH, Gordon S, Edgington TS, Kudryk B, Kreutzer DL, Rickles FR . 1998 Am. J. Pathol. 152: 399–411

  • Sprecher CA, Kisiel W, Mathewes S, Foster DC . 1994 Proc. Natl. Acad. Sci. USA 91: 3353–3357

  • Stephens RW, Pollanen J, Tapiovaara H, Leung KC, Sim PS, Salonen EM, Ronne E, Behrendt N, Dano K, Vaheri A . 1989 J. Cell. Biol. 108: 1987–1995

  • Taniguchi T, Kakkar AK, Tuddenham EG, Williamson RC, Lemoine NR . 1998 Cancer Res. 58: 4461–4467

  • Towbin H, Staehelin T, Gordon J . 1979 Proc. Natl. Acad. Sci. USA 76: 4350–4354

  • Umenishi F, Yasumitsu H, Ashida Y, Yamauti J, Umeda M, Miyazaki K . 1990 J. Biochem. 108: 537–543

  • Vassalli JD, Baccino D, Belin D . 1985 J. Cell. Biol. 100: 86–92

  • Wagner SL, Lau AL, Cunningham DD . 1989 J. Biol. Chem. 264: 611–615

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

  • Yasumitsu H, Miyazaki K, Umenishi F, Koshikawa N, Umeda M . 1992 J. Biochem. 111: 74–80

  • Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R . 1994 Science 263: 526–529

Download references

Acknowledgements

Supported by National Cancer Institute Grants CA-76350, CA-75692, and CA-75557 (JS Rao) and W Kisiel (HL-64119).

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

    Santhi D Konduri, Nirmala Chandrasekar, Anastasia Tasiou, Sanjeeva Mohanam, Yoshiaki Kin, Sajani S Lakka & Jasti S Rao

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

    Dzung Dinh, William C Olivero & Jasti S Rao

  3. Division of Cancer Biology, Department of Neuro-pathology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA

    Meena Gujrati

  4. ZymoGenetics, Inc., Seattle, Washington, USA

    Donald C Foster

  5. University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA

    Walter Kisiel

  6. Center for Prostate Disease Research, Rockville, Maryland, USA

    Chilukuri N Rao

Authors
  1. Santhi D Konduri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chilukuri N Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nirmala Chandrasekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anastasia Tasiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sanjeeva Mohanam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiaki Kin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sajani S Lakka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dzung Dinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. William C Olivero
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Meena Gujrati
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Donald C Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Walter Kisiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. 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

Konduri, S., Rao, C., Chandrasekar, N. et al. A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion. Oncogene 20, 6938–6945 (2001). https://doi.org/10.1038/sj.onc.1204847

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204847

Keywords

This article is cited by

Search

Advanced search

Quick links