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.

  • Short Report
  • Published:

The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells

Oncogene volume 21, pages 6684–6688 (2002)Cite this article

Abstract

Differential gene expression of cell lines derived from a malignant melanoma or its autologous lymph node metastasis using cDNA arrays indicated down-regulation of PRSS11, a gene encoding the serine protease HtrA1, a homolog of the Escherichia coli protease HtrA, in the metastatic line. Stable PRSS11 overexpression in the metastatic cell line strongly inhibited proliferation, chemoinvasion and Nm23-H1 protein expression in vitro, as well as cell growth in vivo in nu/nu mice. A polyclonal anti-HtrA1 serum demonstrated a significantly higher expression in primary melanomas when compared to unrelated metastatic lesions in a human melanoma tissue array, and down-modulation of HtrA1 expression in autologous lymph node melanoma metastases in seven out of 11 cases examined. These results suggest that down-regulation of PRSS11 and HtrA1 expression may represent an indicator of melanoma 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

Similar content being viewed by others

References

  • Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN . 1987 Cancer Res. 47: 3239–3245

  • Baldi A, De Luca A, Claudio PP, Baldi F, Giordano GG, Tommasino M, Paggi MG, Giodano A . 1995 J. Cell. Biochem. 59: 402–408

  • Baldi A, Santini D, Battista T, Dragonetti E, Ferranti G, Petitti T, Groeger AM, Angelini A, Rossiello R, Baldi F, Natali PG, Paggi MG . 2001 J. Cell Biochem. 83: 364–372

  • Berwick M, Halpern A . 1997 Curr. Opin. Oncol. 9: 178–182

  • Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V . 2000 Nature 406: 536–540

  • Burger AM, Zhang Z, Li H, Ostowski JL, Beatty B, Venanzoni M, Papas T, Seth A . 1998 Oncogene 16: 2459–2467

  • Clark EA, Golub TR, Lander ES, Hynes RO . 2000 Nature 406: 532–535

  • Clark Jr WE, Elder DE, Guerry D, Braitman LE, Trock BJ, Schultz D, Synnestvedt M, Halpern AC . 1989 J. Natl. Cancer Inst. 81: 1893–1904

  • Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS . 2000 J. Biol. Chem. 275: 2581–2588

  • Gray CW, Ward RV, Karran E, Turconi S, Rowles A, Viglienghi D, Southan C, Barton A, Fantom KG, West A, Savopoulos J, Hassan NJ, Clinkenbeard H, Hanning C, Amegadzie B, Davies JB, Dingwall C, Livi GP, Creasy CL . 2000 Eur. J. Biochem. 267: 5699–5710

  • Guldberg P, thor Straten P, Birck A, Ahrenkiel V, Kirkin AF, Zeuthen J . 1997 Cancer Res. 57: 3660–3663

  • Hendrix MJ, Seftor EA, Seftor RE, Fidler IJ . 1987 Cancer Lett. 38: 137–147

  • Hu SI, Carozza M, Klein M, Nantermet P, Luk D, Crowl RM . 1998 J. Biol. Chem. 273: 34406–34412

  • Indsto JO, Holland EA, Kefford RF, Mann GJ . 1998 Cancer Genet. Cytogenet. 100: 68–71

  • Kato MV, Sato H, Tsukada T, Ikawa Y, Aizawa S, Nagayoshi M . 1996 Oncogene 12: 1361–1364

  • Krojer T, Garrido-Franco M, Huber R, Ehrmann M, Clausen T . 2002 Nature 416: 455–459

  • Leonetti C, Biroccio A, Candiloro A, Citro G, Fornari C, Mottolese M, Del Bufalo D, Zupi G . 1999 Clin. Cancer Res. 5: 2588–2595

  • Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Almeri ES, Shi Y . 2002 Nat. Struct. Biol. 9: 436–442

  • Lombardi D, Lacombe ML, Paggi MG . 2000 J. Cell. Physiol. 182: 144–149

  • Newton Bishop JA . 1997 Cancer Metastasis Rev. 16: 141–154

  • Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG . 1996 J. Biol. Chem. 271: 30322–30325

  • Pallen MJ, Wren BW . 1997 Mol. Microbiol. 26: 209–221

  • Ponting CP . 1997 Protein Sci. 6: 464–468

  • Robertson GP, Herbst RA, Nagane M, Huang HJ, Cavenee WK . 1999 Cancer Res. 59: 3596–3601

  • Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S, Lee J, Lillie J, Smith DI . 2002 Cancer Res. 62: 262–270

  • Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC . 2001 Arch. Pathol. Lab. Med. 125: 1295–1306

  • Spiess C, Beil A, Ehrmann M . 1999 Cell 97: 339–347

  • Swisshelm K, Ryan K, Tsuchiya K, Sager R . 1995 Proc. Natl. Acad. Sci. USA 92: 4472–4476

  • Zumbrunn J, Trueb B . 1996 FEBS Lett. 398: 187–192

  • Zumbrunn J, Trueb B . 1997 Genomics 45: 461–462

Download references

Acknowledgements

We thank C Leonetti (Regina Elena Institute, Rome, Italy) for providing the LP and LM cell lines, IJ Fidler (MD Anderson Cancer Center, Houston, TX, USA) for the A375P and A375M cell lines, B Trueb (University of Bern, Switzerland) for providing the PRSS11 cDNA, and B Vincenzi (Campus BioMedico University, Rome, Italy) and A Abbate (Catholic University, Rome, Italy) for the statistical analysis. A Baldi is the recipient of a FIRC fellowship. This work was supported in part by AIRC grants to MG Paggi, DM Noonan, A Albini, A Felsani and PG Natali, by FIRC to A De Luca, by Ministero della Sanità to MG Paggi, DM Noonan, A Felsani and D Lombardi, from General Broker Service, Roche and Sanofi Synthelabo grants to A Baldi. We thank AOAR for the continuous support and encouragement.

Author information

Authors and Affiliations

  1. Laboratory ‘C’, CRS, Regina Elena Cancer Institute, Rome, Italy

    Alfonso Baldi, Antonio De Luca, Tullio Battista & Marco G Paggi

  2. National Cancer Research Institute, Genova, Italy

    Monica Morini, Douglas M Noonan & Adriana Albini

  3. CNR, Istituto di Neurobiologia e Medicina Molecolare, Rome, Italy

    Armando Felsani

  4. Department of Biochemistry and Biophysics ‘F. Cedrangolo', Section of Pathology, Second University of Naples, Italy

    Feliciano Baldi

  5. San Gallicano Dermatological Institute, Rome, Italy

    Caterina Catricalà & Ada Amantea

  6. Laboratory of Immunology, CRS, Regina Elena Cancer Institute, Rome, Italy

    Pier Giorgio Natali

  7. Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

    Daniela Lombardi

Authors
  1. Alfonso Baldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monica Morini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tullio Battista
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Armando Felsani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feliciano Baldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Caterina Catricalà
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ada Amantea
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Douglas M Noonan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Adriana Albini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pier Giorgio Natali
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Daniela Lombardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marco G Paggi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco G Paggi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baldi, A., Luca, A., Morini, M. et al. The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells. Oncogene 21, 6684–6688 (2002). https://doi.org/10.1038/sj.onc.1205911

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205911

Keywords

This article is cited by

Search

Advanced search

Quick links