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.

  • Oncogenomics
  • Published:

Gene expression profiles of pancreatic cancer and stromal desmoplasia

Abstract

Gene expression studies were undertaken in normal pancreas and pancreatic adenocarcinomas to determine new candidate genes that can potentially be used as markers of the disease. The characteristic desmoplastic stromal reaction of pancreatic adenocarcinoma greatly hampers expression studies in this tumour type, and usually necessitates time-consuming tissue microdissection for enrichment of the tumour cell population. We show that fine needle aspiration of cancer provides a fast and efficient way of obtaining samples highly enriched in tumour cells with sufficient yields of RNA. Using Atlas cancer cDNA arrays with 588 cancer-related genes, we describe gene expression profiles of normal pancreas, bulk pancreatic tumour tissues and pancreatic tumour aspirates containing more than 95% tumour cells. Analysis of bulk tissue specimens revealed differentially expressed genes belonging predominantly to the stromal component of the tumour. This contrasted with the results obtained from tumour-cell enriched samples. Several genes already described in pancreatic cancer (caspase 8, TIMP1, CD9, IL-13) were also differentially expressed in our study. Furthermore, we found dysregulated expression of genes not previously associated with pancreatic adenocarcinoma, such as Rac 1, GLG1, NEDD5, RPL-13a, RPS9 and members of the Wnt5A gene family. In summary, we present a panel of genes newly identified in the pathogenesis of pancreatic adenocarcinoma and demonstrate that fine needle aspirates of the tumour mass are a convenient source of material for gene expression studies in tumours accompanied by desmoplastic reactions.

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

Access options

Buy this article

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

References

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM . 2000 Nature 403: 503–511

  • Asakura S, Kato H, Fujino S, Konishi T, Tezuka N, Mori A . 1999 Hum. Pathol. 30: 195–198

  • Aspinall RJ, Lemoine NR . 1999 Ann. Oncol. 10: 188–192

  • Berditchevski F, Odintsova E . 1999 J. Cell Biol. 146: 477–492

  • Bramhall SR, Neoptolemos JP, Stamp GW, Lemoine NR . 1997 J. Pathol. 182: 347–355

  • Cardone A, Tolino A, Zarcone R, Borruto Caracciolo G, Tartaglia E . 1997 Panminerva Med. 39: 174–177

  • Chen FW, Davies JP, Ioannou YA . 1998 Mol. Genet. Metab. 64: 271–282

  • Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR, Weiss RA, Liotta LA . 1996 Science 274: 988–1001

  • Fritz G, Just I, Kaina B . 1999 Int. J. Cancer 81: 682–687

  • Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES . 1999 Science 286: 531–537

  • Gress TM, Menke A, Bachem M, Muller-Pillasch F, Ellenrieder V, Weidenbach H, Wagner M, Adler G . 1998 Digestion 59: 625–637

  • Gress TM, Muller-Pillasch F, Geng M, Zimmerhackl F, Zehetner G, Friess H, Buchler M, Adler G, Lehrach H . 1996 Oncogene 13: 1819–1830

  • Gress TM, Muller-Pillasch F, Lerch MM, Friess H, Buchler M, Adler G . 1995 Int. J. Cancer 62: 407–413

  • Gress TM, Wallrapp C, Frohme M, Muller-Pillasch F, Lacher U, Friess H, Buchler M, Adler G, Hoheisel JD . 1997 Genes Chromosomes Cancer 19: 97–103

  • Halvorsen TB, Seim E . 1989 J. Clin. Pathol. 42: 162–166

  • Hu E, Zhu Y, Fredrickson T, Barnes M, Kelsell D, Beeley L, Brooks D . 1998 Biochem. Biophys. Res. Commun. 247: 287–293

  • Iozzo RV, Eichstetter I, Danielson KG . 1995 Cancer Res. 55: 3495–3499

  • Kinoshita M, Kumar S, Mizoguchi A, Ide C, Kinoshita A, Haraguchi T, Hiraoka Y, Noda M . 1997 Genes Dev. 11: 1535–1547

  • Kohl R, Antoine M, Olwin BB, Dickson C, Kiefer P . 2000 J. Biol. Chem. 275: 15741–15748

  • Kornmann M, Kleeff J, Debinski W, Korc M . 1999 Anticancer Res. 19: 125–131

  • Lemoine NR . 1997 Digestion 58: 550–556

  • Lohr M, Schmidt C, Ringel J, Kluth M, Muller P, Nizze H, Jesnowski R . 2001 Cancer Res. 61: 550–555

  • Moscatello D, Santra M, Mann DM, McQuillan DJ, Wong AJ, Iozzo RV . 1998 J. Clin. Invest. 101: 406–412

  • Olson DJ, Gibo DM, Saggers G, Debinski W, Kumar R . 1997 Cell Growth Differ. 8: 417–423

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D . 2000 Nature 406: 747–752

  • Qiu RG, Chen J, Kirn D, McCormick F, Symons M . 1995 Nature 374: 457–459

  • Ricciardelli C, Mayne K, Sykes PJ, Raymond WA, McCaul K, Marshall VR, Horsfall D . 1998 Clin. Cancer Res. 4: 963–971

  • Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO . 2000 Nat. Genet. 24: 227–235

  • Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE . 2001 Cancer Res. 61: 1833–1838

  • Schnelzer A, Prechtel D, Knaus U, Dehne K, Gerhard M, Graeff H, Harbeck N, Schmitt M, Lengyel E . 2000 Oncogene 19: 3013–3020

  • Sho M, Adachi M, Taki T, Hashida H, Konishi T, Huang CL, Ikeda N, Nakajima Y, Kanehiro H, Hisanaga M, Nakano H, Miyake M . 1998 Int. J. Cancer 79: 509–516

  • Shoemaker DD, Schadt EE, Armour CD, He YD, Garrett-Engele P, McDonagh PD, Loerch PM, Leonardson A, Lum PY, Cavet G, Wu LF, Altschuler SJ, Edwards S, King J, Tsang JS, Schimmack G, Schelter JM, Koch J, Ziman M, Marton MJ, Li B, Cundiff P, Ward T, Castle J, Krolewski M, Meyer MR, Mao M, Burchard J, Kidd MJ, Dai H, Phillips JW, Linsley PS, Stoughton R, Scherer S, Boguski MS . 2001 Nature 409: 922–927

  • Sirivatanauksorn V, Sirivatanauksorn Y, Gorman PA, Davidson JM, Sheer D, Moore PS, Scarpa A, Edwards PA, Lemoine NR . 2001 Int. J. Cancer 91: 350–358

  • Sirivatanauksorn Y, Drury R, Crnogorac-Jurcevic T, Sirivatanauksorn V, Lemoine NR . 1999 J. Pathol. 189: 150–154

  • Suwa H, Ohshio G, Imamura T, Watanabe G, Arii S, Imamura M, Narumiya S, Hiai H, Fukumoto M . 1998 Br. J. Cancer 77: 147–152

  • Takaishi K, Sasaki T, Kotani H, Nishioka H, Takai Y . 1997 J. Cell Biol. 139: 1047–1059

  • Virkajarvi N, Paakko P, Soini Y . 1998 Histopathology 33: 432–439

  • Zhang L, Zhou W, Velculescu VE, Kern SE, Hruban RH, Hamilton SR, Vogelstein B, Kinzler KW . 1997 Science 276: 1268–1272

  • Zhou Z, Wang J, Han X, Zhou J, Linder S . 1998 Int. J. Cancer 78: 95–99

Download references

Acknowledgements

Supported by Imperial Cancer Research Fund; Special Trustees of Hammersmith Hospital; Associazione Italiana Ricerca sul Cancro (AIRC) to A Scarpa, Milan, Italy; Consorzio Studi Universitari di Verona, Italy; Ministero Università e Ricerca Scientifica e Tecnologica (MURST), Cofin MM06158571 – Cofin 9906195987, Rome, Italy.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicholas R Lemoine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crnogorac-Jurcevic, T., Efthimiou, E., Capelli, P. et al. Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 20, 7437–7446 (2001). https://doi.org/10.1038/sj.onc.1204935

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204935

Keywords

This article is cited by

Search

Quick links