Abstract
Estrogen-receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that interleukin-8 (IL-8) was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells, and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of IL-8, but not with IL-8 receptor levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by two fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness.
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References
Baggiolini M, Walz A and Kunkel SL . (1989). J. Clin. Invest., 84, 1045–1049.
Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ and Dinney CP . (1999). Clin. Cancer Res., 5, 783–778.
Basolo F, Conaldi PG, Fiore L, Calvo S and Toniolo A . (1993). Int. J. Cancer, 55, 926–930.
Brew R, Erikson JS, West DC, Flanagan BF and Christmas SE . (1997). Biochem. Soc. Trans., 25, 264S.
Brouillet JP, Dujardin MA, Chalbos D, Rey JM, Grenier J, Lamy PJ, Maudelonde T and Pujol P . (2001). Int. J. Cancer, 95, 205–208.
De Larco JE, Wuertz BR, Rosner KA, Erickson SA, Gamache DE, Manivel JC and Furcht LT . (2001). Am. J. Pathol., 158, 639–666.
Fontanini G, Campani D, Roncella M, Cecchetti D, Calvo S, Toniolo A and Basolo F . (1999). Br. J. Cancer, 80, 579–584.
Garcia M, Derocq D, Freiss G and Rochefort H . (1992). Proc. Natl. Acad. Sci. USA, 89, 11538–11542.
Green S and Chambon P . (1986). Nature, 324, 615–617.
Green AR, Green VL, White MC and Speirs V . (1997). Int. J. Cancer, 72, 937–941.
Greene GF, Kitadai Y, Pettaway CA, von Eschenbach AC, Bucana CD and Fidler IJ . (1997). Am. J. Pathol., 150, 1571–1582.
Inoue K, Slaton JW, Eve BY, Kim SJ, Perrotte P, Balbay MD, Yano S, Bar-Eli M, Radinsky R, Pettaway CA and Dinney CP . (2000). Clin. Cancer Res., 6, 2104–2119.
Ivarsson K, Runesson E, Sundfeldt K, Haeger M, Hedin L, Janson PO and Brannstrom M . (1998). Gynecol. Oncol., 71, 420–423.
Lazennec G, Bresson D, Lucas A, Chauveau C and Vignon F . (2001). Endocrinology, 142, 4120–4130.
Lazennec G, Kern L, Valotaire Y and Salbert G . (1997). Mol. Cell. Biol., 17, 5053–5066.
Lee LF, Hellendall RP, Wang Y, Haskill JS, Mukaida N, Matsushima K and Ting JP . (2000). J. Immunol., 164, 2769–2775.
Luca M, Huang S, Gershenwald JE, Singh RK, Reich R, and Bar-Eli M . (1997). Am. J. Pathol., 151, 1105–1113.
Madsen MW and Briand P . (1990). Eur. J. Cancer, 26, 793–797.
Matsushima K and Oppenheim JJ . (1989). Cytokine, 1, 2–13.
McGuire WL . (1975). Cancer, 36, 638–644.
Merogi AJ, Marrogi AJ, Ramesh R, Robinson WR, Fermin CD and Freeman SM . (1997). Hum. Pathol., 28, 321–331.
Miller LJ, Kurtzman SH, Wang Y, Anderson KH, Lindquist RR and Kreutzer DL . (1998). Anticancer Res., 18, 77–81.
Mosselman S, Polman J and Dijkema R . (1996). FEBS Lett., 392, 49–53.
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E and Zlotnik A . (2001). Nature, 410, 50–56.
Nakashima E, Oya A, Kubota Y, Kanada N, Matsushita R, Takeda K, Ichimura F, Kuno K, Mukaida N, Hirose K, Nakanishi I, Ujiie T and Matsushima K . (1996). Pharm. Res., 13, 1896–1901.
Pisani P . (1992). J. Environ Pathol. Toxicol. Oncol., 11, 313–316.
Platet N and Garcia M . (1998). Invasion Metastasis, 18, 198–208.
Pujol P, Rey JM, Nirde P, Roger P, Gastaldi M, Laffargue F, Rochefort H and Maudelonde T . (1998). Cancer Res., 58, 5367–5373.
Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P and Rochefort H (2001). Cancer Res., 61, 2537–2541.
Schadendorf D, Moller A, Algermissen B, Worm M, Sticherling M and Czarnetzki BM . (1993). J. Immunol., 151, 2667–2675.
Skoog L, Humla S, Axelsson M, Frost M, Norman A, Nordenskjold B and Wallgren A . (1987). Acta Oncol., 26, 95–100.
Sommers CL, Byers SW, Thompson EW, Torri JA and Gelmann EP . (1994). Breast Cancer Res. Treat., 31, 325–335.
Speirs V, Green AR and White MC . (1996). Int. J. Cancer, 66, 551–556.
Sprenger H, Lloyd AR, Lautens LL, Bonner TI and Kelvin DJ . (1994a). J. Biol. Chem., 269, 11065–11072.
Sprenger H, Lloyd AR, Meyer RG, Johnston JA and Kelvin DJ (1994b) J. Immunol., 153, 2524–2532.
Terui Y, Ikeda M, Tomizuka H, Kasahara T, Ohtsuki T, Uwai M, Mori M, Itoh T, Tanaka M, Yamada M, Shimamura S, Ishizaka Y, Ikeda K, Ozawa K, Miura Y and Hatake K . (1998). Blood, 92, 2672–2680.
Terui Y, Tomizuka H, Mishima Y, Ikeda M, Kasahara T, Uwai M, Mori M, Itoh T, Tanaka M, Yamada M, Shimamura S, Ishizaka Y, Ozawa K and Hatake K . (1999). Cancer Res., 59, 5651–5655.
Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S and Lippman ME . et al. (1992). J. Cell Physiol., 150, 534–544.
Veltri RW, Miller MC, Zhao G, Ng A, Marley GM, Wright Jr GL, Vessella RL and Ralph D . (1999). Urology, 53, 139–147.
Xu L and Fidler IJ . (2000). Oncol. Res., 12, 97–106.
Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD and Fidler IJ . (1998). J. Natl. Cancer Inst., 90, 447–454.
Youngs SJ, Ali SA, Taub DD and Rees RC . (1997). Int. J. Cancer, 71, 257–266.
Acknowledgements
We thank Dr T Maudelonde for a critical reading of the manuscript and Professor J P Daures for statistical analysis. We thank the Vector Core of the University Hospital of Nantes supported by the Association Francaise contre les Myopathies (AFM) for the production of Adenoviruses. This work was supported by grants from ARC (Association pour la Recherche contre le Cancer, Grant No. 4302), la Ligue Nationale contre le Cancer (Comite du Gard), INSERM and CNRS.
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Freund, A., Chauveau, C., Brouillet, JP. et al. IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells. Oncogene 22, 256–265 (2003). https://doi.org/10.1038/sj.onc.1206113
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DOI: https://doi.org/10.1038/sj.onc.1206113
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