The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression

  • Authors:
    • Alexander G. Pantschenko
    • Irina Pushkar
    • Kathleen H. Anderson
    • Yanping Wang
    • Lauri J. Miller
    • Scott H. Kurtzman
    • George Barrows
    • Donald L. Kreutzer
  • View Affiliations

  • Published online on: August 1, 2003     https://doi.org/10.3892/ijo.23.2.269
  • Pages: 269-284
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

We have previously described the expression of interleukin cytokines (IL)-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra) in human breast cancer (HBC) tissue. Based on our previous studies, we hypothesize that the IL-1 family of cytokines, antagonists (IL-1ra) and receptors (IL-1RI and IL-1RII) are present within the human breast cancer (HBC) tumor microenvironment and that the IL-1 network of cytokines and receptors within the tumor microenvironment can control tumor cell subpopulation expression of other protumorigenic cytokines such as the angiogenic/growth factor, interleukin-8 (IL-8). To test this hypothesis we characterized the in vivo expression of the IL-1 network in HBC tissues and homogenates by immunohistochemistry (IHC) and ELISA. Additionally, we examined IL-1R expression in HBC cell lines in vitro and in a murine xenograft model by IHC. Finally, we determined the ability of IL-1 to induce IL-8 expression in in vitro using HBC cell lines. We observed that not only are the IL-1 cytokines present in HBC tissue and homogenates, but that IL-1Rs and IL-8 are also present in the HBC tumor microenvironment. Additionally, expression levels for some members of the IL-1/IL-8 network of cytokines correlated with the prognostic indicators, ER/PR. Using HBC cell lines, we observed that HBC cell lines express IL-1Rs in vitro and in the xenograft model. Furthermore, in vitro, HBC cell lines show a spectrum of responsiveness to IL-1 as measured by expression the proangiogenic/mitogenic cytokine IL-8. Our data clearly demonstrate the presence and distribution of IL-1 cytokines and receptors in HBC and suggests that the local expression of IL-1 results in the activation of a population of cells within the HBC tumor microenvironment. This activation of the IL-1/IL-1R cytokine family via autocrine and/or paracrine mechanisms leads to a cascade of secondary protumorigenic cytokines. These secondary signals induce the expression of numerous protumorigenic activities such as the expression of IL-8, and subsequently contribute to angiogenesis, tumor proliferation, and tumor invasion.

Related Articles

Journal Cover

August 2003
Volume 23 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Pantschenko AG, Pushkar I, Anderson KH, Wang Y, Miller LJ, Kurtzman SH, Barrows G and Kreutzer DL: The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression. Int J Oncol 23: 269-284, 2003.
APA
Pantschenko, A.G., Pushkar, I., Anderson, K.H., Wang, Y., Miller, L.J., Kurtzman, S.H. ... Kreutzer, D.L. (2003). The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression. International Journal of Oncology, 23, 269-284. https://doi.org/10.3892/ijo.23.2.269
MLA
Pantschenko, A. G., Pushkar, I., Anderson, K. H., Wang, Y., Miller, L. J., Kurtzman, S. H., Barrows, G., Kreutzer, D. L."The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression". International Journal of Oncology 23.2 (2003): 269-284.
Chicago
Pantschenko, A. G., Pushkar, I., Anderson, K. H., Wang, Y., Miller, L. J., Kurtzman, S. H., Barrows, G., Kreutzer, D. L."The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression". International Journal of Oncology 23, no. 2 (2003): 269-284. https://doi.org/10.3892/ijo.23.2.269