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Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells

Oncogene volume 24, pages 3512–3524 (2005)Cite this article

Abstract

A hallmark of plasma cells is the expression of syndecan-1, which has major functions in epithelial cells, in particular as the coreceptor of heparin-binding growth factors. We previously found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a growth factor for malignant plasma cells. As amphiregulin (AREG) is another heparin-binding factor of the EGF family, we investigated its role in multiple myeloma (MM). Using Affymetrix DNA microarrays, we show here that the AREG gene was expressed by purified primary myeloma cells from 65 patients and that the expression was higher than in normal bone marrow (BM) plasma cells or plasmablastic cells. AREG stimulated IL-6 production and growth of BM stromal cells. Using real-time reverse transcriptase–polymerase chain reaction, we found that MM cells expressed ErbB receptors and that AREG promoted their growth. Furthermore, PD169540 (a pan-ErbB inhibitor) and IRESSA (an ErbB1-specific inhibitor) induced apoptosis of primary myeloma cells from 10/14 and 4/14 patients, respectively, and there was a synergistic effect with dexamethasone. Altogether, our data provide strong evidence that AREG plays an important role in the biology of MM and emphasize the advantages of using ErbB inhibitors, which might target myeloma cells as well as the tumor environment.

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References

  • Alimandi M, Wang LM, Bottaro D, Lee CC, Kuo A, Frankel M, Fedi P, Tang C, Lippman M and Pierce JH . (1997). EMBO J., 16, 5608–5617.

  • Badache A and Hynes NE . (2001). Cancer Res., 61, 383–391.

  • Boucheix C and Rubinstein E . (2001). Cell Mol. Life Sci., 58, 1189–1205.

  • Claudio JO, Masih-Khan E, Tang H, Goncalves J, Voralia M, Li ZH, Nadeem V, Cukerman E, Francisco-Pabalan O, Liew CC, Woodgett JR and Stewart AK . (2002). Blood, 100, 2175–2186.

  • Costes V, Magen V, Legouffe E, Durand L, Baldet P, Rossi JF, Klein B and Brochier J . (1999). Hum. Pathol., 30, 1405–1411.

  • Couchman JR . (2003). Nat. Rev. Mol. Cell. Biol., 4, 926–937.

  • De Vos J, Couderc G, Tarte K, Jourdan M, Requirand G, Delteil MC, Rossi JF, Mechti N and Klein B . (2001). Blood, 98, 771–780.

  • Gu ZJ, De Vos J, Rebouissou C, Jourdan M, Zhang XG, Rossi JF, Wijdenes J and Klein B . (2000). Leukemia, 14, 188–197.

  • Harris RC, Chung E and Coffey RJ . (2003). Exp. Cell Res., 284, 2–13.

  • Holbro T, Civenni G and Hynes NE . (2003). Exp. Cell Res., 284, 99–110.

  • Hynes NE, Horsch K, Olayioye MA and Badache A . (2001). Endocr. Relat. Cancer, 8, 151–159.

  • Inui S, Higashiyama S, Hashimoto K, Higashiyama M, Yoshikawa K and Taniguchi N . (1997). J. Cell Physiol., 171, 291–298.

  • Iwamoto R and Mekada E . (2000). Cytokine Growth Factor Rev., 11, 335–344.

  • Jourdan M, De Vos J, Mechti N and Klein B . (2000). Cell Death Differ., 7, 1244–1252.

  • Jourdan M, Zhang XG, Portier M, Boiron JM, Bataille R and Klein B . (1991). J. Immunol., 147, 4402–4407.

  • Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoka H, Tang B, Tanabe O, Tanaka H, Kuramoto A and Kishimoto T . (1988). Nature, 332, 83–85.

  • Klein B, Tarte K, Jourdan M, Mathouk K, Moreaux J, Jourdan E, Legouffe E, De Vos J and Rossi JF . (2003). Int. J. Hematol., 78, 106–113.

  • Klein B, Zhang XG, Jourdan M, Content J, Houssiau F, Aarden L, Piechaczyk M and Bataille R . (1989). Blood, 73, 517–526.

  • Lu ZY, Brailly H, Wijdenes J, Bataille R, Rossi JF and Klein B . (1995a). Blood, 86, 3123–3131.

  • Lu ZY, Zhang XG, Rodriguez C, Wijdenes J, Gu ZJ, Morel-Fournier B, Harousseau JL, Bataille R, Rossi JF and Klein B . (1995b). Blood, 85, 2521–2527.

  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J and Haber DA . (2004). N. Engl. J. Med., 350, 2129–2139.

  • Mahtouk K, Jourdan M, De Vos J, Hertogh C, Fiol G, Jourdan E, Rossi JF and Klein B . (2004). Blood, 103, 1829–1837.

  • Manegold C . (2003). Adv. Exp. Med. Biol., 532, 247–252.

  • Nylander N, Smith LT, Underwood RA and Piepkorn M . (1998). In Vitro Cell Dev. Biol. Anim., 34, 182–188.

  • Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE and Meyerson M . (2004). Science, 304, 1497–1500.

  • Qiu Y, Ravi L and Kung HJ . (1998). Nature, 393, 83–85.

  • Rapraeger AC . (2000). J. Cell Biol., 149, 995–998.

  • Rebouissou C, Wijdenes J, Autissier P, Tarte K, Costes V, Liautard J, Rossi JF, Brochier J and Klein B . (1998). Blood, 91, 4727–4737.

  • Sakuma T, Higashiyama S, Hosoe S, Hayashi S and Taniguchi N . (1997). J. Biochem. (Tokyo), 122, 474–480.

  • Shao J, Lee SB, Guo H, Evers BM and Sheng H . (2003). Cancer Res., 63, 5218–5223.

  • Tarte K, Fiol G, Legouffe E, Rossi JF and Klein B . (2000). Blood, 96, 514a.

  • Trikha M, Corringham R, Klein B and Rossi JF . (2003). Clin. Cancer Res., 9, 4653–4665.

  • Uchiyama H, Barut BA, Mohrbacher AF, Chauhan D and Anderson KC . (1993). Blood, 82, 3712–3720.

  • Walters D, French J, Arendt B and Jelinek D . (2003). Oncogene, 22, 3598–3607.

  • Wang LM, Kuo A, Alimandi M, Veri MC, Lee CC, Kapoor V, Ellmore N, Chen XH and Pierce JH . (1998). Proc. Natl. Acad. Sci USA, 95, 6809–6814.

  • Wang YD, De Vos J, Jourdan M, Couderc G, Lu ZY, Rossi JF and Klein B . (2002). Oncogene, 21, 2584–2592.

  • Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, van Rhee F, Fassas A, Crowley J, Tricot G, Barlogie B and Shaughnessy Jr J . (2002). Blood, 99, 1745–1757.

  • Zhang XG, Gaillard JP, Robillard N, Lu ZY, Gu ZJ, Jourdan M, Boiron JM, Bataille R and Klein B . (1994). Blood, 83, 3654–3663.

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Acknowledgements

This work was supported by grants from the Ligue Nationale Contre le Cancer (équipe labellisée), Paris, France, and from the Association Guillaume Espoir, St Genis Laval, France.

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Authors and Affiliations

  1. INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, Hôpital St Eloi, 34000, Montpellier, France

    Karène Mahtouk, Thierry Rème, John De Vos, Michel Jourdan, Jérôme Moreaux, Geneviève Fiol, Véronique Grau & Bernard Klein

  2. Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, INF410, 69115, Heidelberg, Germany

    Dirk Hose, Marc Raab, Marion Moos, Hartmut Goldschmidt & Friedrich W Cremer

  3. Internal Medicine Department B, CHU Nîmes, 30900, Nîmes, France

    Eric Jourdan

  4. Clinical Hematology Department, CHU Montpellier, Hôpital Lapeyronie, 34000, Montpellier, France

    Marion Baudard & Jean François Rossi

  5. Institut für Humangenetik, Universitätsklinikum Heidelberg, INF 366, 69120, Heidelberg, Germany

    Friedrich W Cremer

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  1. Karène Mahtouk
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Correspondence to Bernard Klein.

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Mahtouk, K., Hose, D., Rème, T. et al. Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells. Oncogene 24, 3512–3524 (2005). https://doi.org/10.1038/sj.onc.1208536

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