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Immune responses to all ErbB family receptors detectable in serum of cancer patients

Oncogene volume 18, pages 1267–1275 (1999)Cite this article

Abstract

Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-specific immunoprecipitates. Positive sera contained ErbB-specific antibodies of the IgG isotype. Representative immuno-histochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in five of six patients. These findings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.

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References

  • Aaronson SA. . 1991 Science 254: 1146–1153.

  • Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson S, Di Fiore PP and Kraus MH. . 1995 Oncogene 10: 1813–1821.

  • Baselga J, Tripanthy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddel T, Henderson IC and Norton L. . 1996 J. Clin. Oncol. 14: 737–744.

  • Baulida J, Kraus MH, Alimandi M, Di Fiore PP and Carpenter G. . 1996 J. Biol. Chem. 271: 5251–5257.

  • Brice EC, Wu JX, Muraro R, Adamson ED and Willey LM. . 1993 Devel. Genetics 14: 174–184.

  • Burden S and Yarden Y. . 1997 Neuron 18: 847–855.

  • Carraway III KL and Cantley LC. . 1994 Cell 78: 5–8.

  • Cebra JJ, Komisar JL and Schweitzer PA. . 1984 Annu. Rev. Immunol. 2: 493–548.

  • Cibotti R, Kannellopoulus JM, Cabalions JP, Halle-Panenko O, Kosmatopoulus K, Sercarz E and Kourilsky P. . 1992 Proc. Natl. Acad. Sci. USA 89: 416–420.

  • Clark MA, Hawking NJ, Papaioannou A, Fiddes RJ and Ward RL. . 1997 Clin. Exp. Immunol. 109: 166–174.

  • Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR, Schlessinger J and Aaronson SA. . 1987a Cell 51: 1063–1070.

  • Di Fiore PP, Pierce JH, Kraus MH, Segatto O, King CR and Aaronson SA. . 1987b Science 237: 178–182.

  • Di Fiore PP and Kraus MH. . 1991 Genes, oncogenes and hormones: Advances in cellular and molecular biology of breast cancer. Dickson RB and Lipman ME (eds).. Kluwer Academic Publishers: Boston pp.139–160.

    Book  Google Scholar 

  • Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB, Moe R and Cheever MA. . 1994a Cancer Res. 54: 16–20.

  • Disis ML, Smith JW, Murphy AE, Chen W and Cheever MA. . 1994b Cancer Res. 54: 1071–1076.

  • Disis M, Gralow JR, Bernhard H, Hand SL, Rubin WD and Cheever MA. . 1996 J. Immunology 156: 3151–3158.

  • Disis ML, Pupa SL, Grawlow JR, Dittadi R, Menard S and Cheever MA. . 1997 J. Clin. Oncol. 15: 3363–3367.

  • Fedi P, Pierce JH, Di Fiore PP and Kraus MH. . 1994 Mol. Cell. Biol. 14: 492–500.

  • Fisk B, Blevins TL, Wharton JT and Ioannides CG. . 1995 J. Exp. Med. 181: 2109–2117.

  • Glushkov AN, Anosova TP, Anosov MP, Garmanchouk LV and Pogrebnoy PV. . 1996 Exp. Oncology 18: 81–83.

  • Hynes NE and Stern DF. . 1994 Biochim. Biophys. Acta 1198: 165–184.

  • King CR, Borrello I, Bellot F, Comoglio P and Schlessinger J. . 1988 EMBO J. 7: 1647–1651.

  • Kokai Y, Myers JN, Brown VI, LeVea CM, Davis JG, Dobashi K and Greene MI. . 1989 Cell 58: 287–292.

  • Kraus MH, Popescu NC, Amsbaugh C and King CR. . 1987 EMBO J. 6: 605–610.

  • Kraus MH, Issing W, Miki T, Popescu NC and Aaronson SA. . 1989 Proc. Natl. Acad. Sci. USA 86: 9193–9197.

  • Kraus MH, Fedi P, Starks V, Muraro R and Aaronson SA. . 1993 Proc. Natl. Acad. Sci. USA 90: 2900–2904.

  • Lubin R, Zalcman G, Bouchet L, Tredanel J, Legros Y, Cazals D, Hirsch A and Soussi T. . 1995 Nat. Med. 1: 701–702.

  • Mariani Costantini R, Muraro R, Ficari F, Valli C, Bei R, Tonelli F, Caramia F and Frati L. . 1991 Cancer 67: 2880–2886.

  • Nagata Y, Furugen R, Hiasa A, Ikeda H, Ohta N, Furukawa K, Nakamura H, Furukawa K, Kanematsu T and Shiku H. . 1997 J. Immunol. 159: 1336–1343.

  • Nanda NK and Sercarz EE. . 1995 Cell 82: 13–17.

  • Peoples GE, Goedegebuur PS, Smith R, Linehan DC, Yoshino I and Eberlein TJ. . 1995 Proc. Natl. Acad. Sci. USA 92: 432–436.

  • Pinkas-Kramarsky R, Soussan L, Waterman H, Levkowitz G, Alroy I, Klapper L, Lavi S, Seger R, Ratzkin BJ, Sela M and Yarden Y. . 1996 EMBO J. 15: 2452–2467.

  • Pupa SM, Menard S, Andreola S and Colnaghi MI. . 1993 Cancer Res. 53: 5864–5866.

  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A and Press MF. . 1989 Science 244: 707–712.

  • Tuttle TM. . 1996 Cancer Immunol. Immunother. 43: 135–141.

  • Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, Downward J, Mayes EL, Whittle N, Waterfield MD and Seeburg PH. . 1984 Nature 309: 418–425.

  • van der Geer P, Hunter T and Lindberg RA. . 1994 Annu. Rev. Cell Biol. 10: 251–337.

  • Vecchi M, Baulida J and Carpenter G. . 1996 J. Biol. Chem. 271: 18989–18995.

  • Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T and Toyoshima K. . 1986 Nature 319: 230–234.

  • Zafiropoulos A, Andersson E, Krambovitis E and Borrebaeck CA. . 1997 J. Immunol. Methods 200: 181–190.

  • Zhang K, Liu N, Wen D, Chang D, Thomanson A and Yoshinaga SK. . 1996 J. Biol. Chem. 271: 3884–3890.

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Acknowledgements

The authors thank Dr Angelo Del Nero, University `La Sapienza', Rome, for statistical analyses. This study was partly supported by grants from the Ministero dell'Universita' e della Ricerca Scientifica (MURST), the Consiglio Nazionale delle Ricerche (project CNR-ACRO), the Associazione Italiana per la ricerca sul Cancro (AIRC) and the European Community (Programme-Biomed II).

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Authors and Affiliations

  1. Department of Experimental Medicine and Pathology, University `La Sapienza', Rome, Italy

    Roberto Bei, Laura Masuelli, Enrica Moriconi, Vincenzo Visco & Anna Moretti

  2. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    Matthias H Kraus

  3. Department of Oncology and Neurosciences, University `G D'Annunzio', Chieti, Italy

    Raffaella Muraro

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  1. Roberto Bei
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Bei, R., Masuelli, L., Moriconi, E. et al. Immune responses to all ErbB family receptors detectable in serum of cancer patients. Oncogene 18, 1267–1275 (1999). https://doi.org/10.1038/sj.onc.1202442

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