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. 1992 Oct;66(4):712–716. doi: 10.1038/bjc.1992.343

Interleukin-4 receptor and epidermal growth factor receptor expression in colorectal cancer.

L Kaklamanis 1, K C Gatter 1, N Mortensen 1, A L Harris 1
PMCID: PMC1977405  PMID: 1419612

Abstract

Interleukin-4 receptor (IL-4R) and Epidermal Growth Factor receptor (EGFR) were assessed as factors associated with adenoma-carcinoma progression in colorectal cancer and tumour invasion. A monoclonal antibody (MR6) was applied to detect IL-4R in: metaplastic polyps (five cases), adenomas (15 cases), and carcinomas (44 adenocarcinomas and one squamous cell). Positive labelling was obtained in all polyps, adenomas and in 40/45 carcinomas. Normal colonic mucosa of these patients, as well as macrophages and lymphocytes infiltrating the tumour stroma, were also positively labelled with MR6. Four out of five poorly differentiated adenocarcinomas did not show IL-4 receptor expression. No significant correlation was found with tumour size, lymph node stage and IL-4 receptor expression. On the above specimens a parallel detection of epidermal growth factor receptors (EGFR) by a monoclonal antibody (EGFR 1) was carried out. Expression of EGFR was found in 14/20 polyps and in 22/45 carcinomas. All but one of the EGFR positive malignant tumours showed coexpression of IL-4 receptor. Lymph node involvement by tumour cells was detected in 25 out of 45 patients. Eighteen of these 25 cases were positive with EGFR1.

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Selected References

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  1. Al Jabaari B., Ladyman H. M., Larché M., Sivolapenko G. B., Epenetos A. A., Ritter M. A. Elevated expression of the interleukin 4 receptor in carcinoma: a target for immunotherapy? Br J Cancer. 1989 Jun;59(6):910–914. doi: 10.1038/bjc.1989.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anzano M. A., Rieman D., Prichett W., Bowen-Pope D. F., Greig R. Growth factor production by human colon carcinoma cell lines. Cancer Res. 1989 Jun 1;49(11):2898–2904. [PubMed] [Google Scholar]
  3. Benveniste E. N., Merrill J. E. Stimulation of oligodendroglial proliferation and maturation by interleukin-2. Nature. 1986 Jun 5;321(6070):610–613. doi: 10.1038/321610a0. [DOI] [PubMed] [Google Scholar]
  4. Berger M. S., Gullick W. J., Greenfield C., Evans S., Addis B. J., Waterfield M. D. Epidermal growth factor receptors in lung tumours. J Pathol. 1987 Aug;152(4):297–307. doi: 10.1002/path.1711520408. [DOI] [PubMed] [Google Scholar]
  5. Coffey R. J., Jr, Goustin A. S., Soderquist A. M., Shipley G. D., Wolfshohl J., Carpenter G., Moses H. L. Transforming growth factor alpha and beta expression in human colon cancer lines: implications for an autocrine model. Cancer Res. 1987 Sep 1;47(17):4590–4594. [PubMed] [Google Scholar]
  6. Coffey R. J., Jr, Shipley G. D., Moses H. L. Production of transforming growth factors by human colon cancer lines. Cancer Res. 1986 Mar;46(3):1164–1169. [PubMed] [Google Scholar]
  7. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  8. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  9. Fernandez-Botran R., Krammer P. H., Diamantstein T., Uhr J. W., Vitetta E. S. B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines. J Exp Med. 1986 Aug 1;164(2):580–593. doi: 10.1084/jem.164.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gaffney E. V., Tsai S. C. Lymphocyte-activating and growth-inhibitory activities for several sources of native and recombinant interleukin 1. Cancer Res. 1986 Aug;46(8):3834–3837. [PubMed] [Google Scholar]
  11. Gallo-Payet N., Hugon J. S. Epidermal growth factor receptors in isolated adult mouse intestinal cells: studies in vivo and in organ culture. Endocrinology. 1985 Jan;116(1):194–201. doi: 10.1210/endo-116-1-194. [DOI] [PubMed] [Google Scholar]
  12. Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
  13. Gullick W. J., Marsden J. J., Whittle N., Ward B., Bobrow L., Waterfield M. D. Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res. 1986 Jan;46(1):285–292. [PubMed] [Google Scholar]
  14. Hidalgo I. J., Kato A., Borchardt R. T. Binding of epidermal growth factor by human colon carcinoma cell (Caco-2) monolayers. Biochem Biophys Res Commun. 1989 Apr 14;160(1):317–324. doi: 10.1016/0006-291x(89)91658-6. [DOI] [PubMed] [Google Scholar]
  15. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Larche M., Lamb J. R., O'Hehir R. E., Imami-Shita N., Zanders E. D., Quint D. E., Moqbel R., Ritter M. A. Functional evidence for a monoclonal antibody that binds to the human IL-4 receptor. Immunology. 1988 Dec;65(4):617–622. [PMC free article] [PubMed] [Google Scholar]
  17. Larché M., Lamb J. R., Ritter M. A. A novel T-lymphocyte molecule that may function in the induction of self-tolerance and MHC-restriction within the human thymic microenvironment. Immunology. 1988 May;64(1):101–105. [PMC free article] [PubMed] [Google Scholar]
  18. Libermann T. A., Razon N., Bartal A. D., Yarden Y., Schlessinger J., Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984 Feb;44(2):753–760. [PubMed] [Google Scholar]
  19. Mat I., Larche M., Melcher D., Ritter M. A. Tumour-associated upregulation of the IL-4 receptor complex. Br J Cancer Suppl. 1990 Jul;10:96–98. [PMC free article] [PubMed] [Google Scholar]
  20. Mortarini R., Belli F., Parmiani G., Anichini A. Cytokine-mediated modulation of HLA-class II, ICAM-1, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIL1-beta, rTNF-alpha, rIFN-gamma, rIL4 and their combinations. Int J Cancer. 1990 Feb 15;45(2):334–341. doi: 10.1002/ijc.2910450221. [DOI] [PubMed] [Google Scholar]
  21. Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Murthy U., Anzano M. A., Greig R. G. Expression of TGF-alpha/EGF and TGF-beta receptors in human colon carcinoma cell lines. Int J Cancer. 1989 Jul 15;44(1):110–115. doi: 10.1002/ijc.2910440120. [DOI] [PubMed] [Google Scholar]
  23. Neal D. E., Smith K., Fennelly J. A., Bennett M. K., Hall R. R., Harris A. L. Epidermal growth factor receptor in human bladder cancer: a comparison of immunohistochemistry and ligand binding. J Urol. 1989 Mar;141(3):517–521. doi: 10.1016/s0022-5347(17)40877-9. [DOI] [PubMed] [Google Scholar]
  24. Nicholson S., Sainsbury J. R., Halcrow P., Chambers P., Farndon J. R., Harris A. L. Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer. Lancet. 1989 Jan 28;1(8631):182–185. doi: 10.1016/s0140-6736(89)91202-6. [DOI] [PubMed] [Google Scholar]
  25. O'Garra A. Interleukins and the immune system 1. Lancet. 1989 Apr 29;1(8644):943–947. [PubMed] [Google Scholar]
  26. O'Garra A. Interleukins and the immune system 2. Lancet. 1989 May 6;1(8645):1003–1005. doi: 10.1016/s0140-6736(89)92640-8. [DOI] [PubMed] [Google Scholar]
  27. Ohara J., Paul W. E. Receptors for B-cell stimulatory factor-1 expressed on cells of haematopoietic lineage. Nature. 1987 Feb 5;325(6104):537–540. doi: 10.1038/325537a0. [DOI] [PubMed] [Google Scholar]
  28. Park L. S., Friend D., Sassenfeld H. M., Urdal D. L. Characterization of the human B cell stimulatory factor 1 receptor. J Exp Med. 1987 Aug 1;166(2):476–488. doi: 10.1084/jem.166.2.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Phillips J. O., Everson M. P., Moldoveanu Z., Lue C., Mestecky J. Synergistic effect of IL-4 and IFN-gamma on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells. J Immunol. 1990 Sep 15;145(6):1740–1744. [PubMed] [Google Scholar]
  30. Pérez R., Pascual M., Macías A., Lage A. Epidermal growth factor receptors in human breast cancer. Breast Cancer Res Treat. 1984;4(3):189–193. doi: 10.1007/BF01806484. [DOI] [PubMed] [Google Scholar]
  31. Rennick D., Yang G., Muller-Sieburg C., Smith C., Arai N., Takabe Y., Gemmell L. Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6889–6893. doi: 10.1073/pnas.84.19.6889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rodeck U., Herlyn M., Herlyn D., Molthoff C., Atkinson B., Varello M., Steplewski Z., Koprowski H. Tumor growth modulation by a monoclonal antibody to the epidermal growth factor receptor: immunologically mediated and effector cell-independent effects. Cancer Res. 1987 Jul 15;47(14):3692–3696. [PubMed] [Google Scholar]
  33. Rodrigues N. R., Rowan A., Smith M. E., Kerr I. B., Bodmer W. F., Gannon J. V., Lane D. P. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. doi: 10.1073/pnas.87.19.7555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rothbauer E., Mann K., Wiebecke B., Borlinghaus P., Lamerz R., Pratschke E., Krämling H. J., Pfeiffer A. Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas. Klin Wochenschr. 1989 May 15;67(10):518–523. doi: 10.1007/BF01719776. [DOI] [PubMed] [Google Scholar]
  35. Sainsbury J. R., Farndon J. R., Needham G. K., Malcolm A. J., Harris A. L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet. 1987 Jun 20;1(8547):1398–1402. doi: 10.1016/s0140-6736(87)90593-9. [DOI] [PubMed] [Google Scholar]
  36. Stuart P. M., Zlotnik A., Woodward J. G. Induction of class I and class II MHC antigen expression on murine bone marrow-derived macrophages by IL-4 (B cell stimulatory factor 1). J Immunol. 1988 Mar 1;140(5):1542–1547. [PubMed] [Google Scholar]
  37. Tepper R. I., Pattengale P. K., Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  38. Tungekar M. F., Turley H., Dunnill M. S., Gatter K. C., Ritter M. A., Harris A. L. Interleukin 4 receptor expression on human lung tumors and normal lung. Cancer Res. 1991 Jan 1;51(1):261–264. [PubMed] [Google Scholar]
  39. Veale D., Kerr N., Gibson G. J., Harris A. L. Characterization of epidermal growth factor receptor in primary human non-small cell lung cancer. Cancer Res. 1989 Mar 1;49(5):1313–1317. [PubMed] [Google Scholar]
  40. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  41. Waterfield M. D., Mayes E. L., Stroobant P., Bennet P. L., Young S., Goodfellow P. N., Banting G. S., Ozanne B. A monoclonal antibody to the human epidermal growth factor receptor. J Cell Biochem. 1982;20(2):149–161. doi: 10.1002/jcb.240200207. [DOI] [PubMed] [Google Scholar]
  42. de Maagd R. A., MacKenzie W. A., Schuurman H. J., Ritter M. A., Price K. M., Broekhuizen R., Kater L. The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. Immunology. 1985 Apr;54(4):745–754. [PMC free article] [PubMed] [Google Scholar]

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